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328 Cards in this Set
- Front
- Back
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role of gut-associated lymphatic tissue (GALT)
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protect against potential microbial pathogens; permit immunologic tolerance to both potentially immunogenc dietary substances & bacteria that normally reside in the lumen.
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describe immune system via Peyer's Patches
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M cells take up antigens; in germinal cells, B cells stimulated -> differentiate into IgA-secreting plasma cells
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name "one-alphabet-named" cells and what they secrete in small intestine
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I cell: CCK; K cell: GIP; S cell: secretin; D cells: somatostatin
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role of CCK; where and when is it secreted?
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stimulate pancreatic enzyme secretion, gallbladder secretion, satiety factor; decreaes gastric emptying; secreted in duodenum & jejunum in response to presence of lipids & partially digested proteins; activated by gastrin
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role of GIP (gastric inhibitory peptide)
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stimulate insulin reliease, inhibits gastrin & gastric acid release when lipids reach duodenum ; response to duodenal glucose;
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what activates parietal cells, and what inhibits it?
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activated by histamine, ACh, gastrin; decreased by somatostatin, GIP, prostaglandins
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role of secretin; when?
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stimulates pancreatic bicarbonate, bile acid, fluid secretion; decreases gastric acid secretion when lipids enter duodenum & when chyme pH is low
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role of somatostatin; when?
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inhibits gastrin & pepsinogen release; inhibits bile flow/ gallbladder contraction, inhibits pancreatic endocrine & exocrine secretions, increase intestinal fluid absorption & smooth m. contraction, inhibits intestinal secretion; secreted in response to acid, inhibited by vagus n. (pretty much inhibits all GI secretions, activates absorption)
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role of cimetidine, rantidine, famotidine
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reversible block of H2 receptors (affect of histamine); potent inhibitor of p450 system.
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role of omeprazole, lansoprazole
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irreversibly inhibit H+/ K+ ATPase pump
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role of misoprostol
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prostaglandin analogue
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role of pirenzepine, propantheline
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muscarinic antagonist; block the activation of ECL cells and parietal cells by vagus nerve
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role of calcium carbonate, aluminum OH
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antacid
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role of infliximab
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monoclonal antibody of TNF; anti-inflammatory
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role of sulfasalazine
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combo of antibiotics and anti-inflammatory;
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role of 5ASA
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anti-inflammatory
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role of ondansetron
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5HT3 antagonist; anti-emetic
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role of metoclopramide
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D2 receptor antagonist; anti-emetic; increase resting tone for LES - for diabetic & post-surgery gastroparesis; treatment for gastricstasis
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role of ciprofloxacin
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blocks bacterial DNA synthesis (antibiotics)
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what's in saliva?
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salt, water, mucins, IgA, DNAase, lysozyme, lipase, alpha-amylase
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what's special about salivary gland innervation
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stimulated by both sympathetic & parasympathetic activity
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affect of flow rate for salivary content
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low flow rate: hypotonic, rich in K+; high flow rate: isotonic; fast flow: sodium, chloride, HCO3 go up (not absorbed as much; HCO3 not secreted until activated)
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mechanism of salivary ducts
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absorb sodium, chloride; not water; secrete HCO3, K+
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Sjogren syndrome
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autoimmune disease; inhibit salivary secretions; xerostomia (dry mouth)
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two types of peristalsis by esophagus
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primary: initiated by swallowing; secondarY: elicited by distention to clear remaining fo od
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phases of swallowing reflex; and regulation of LES relax'n
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oral (voluntary), pharyngeal (involuntary), esophageal (involuntary); VIP and NO activate LES relax'n, ACh inhibit it
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tx to esophageal varices
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treat hypertension; surgical shunt to divert blood to systemic circulation
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achalasia: ID
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LES doesn't fully relax
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achalasia: etiology, pathophysiology
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possibly autoimmune attack-> degeneration of nerve ganglia in myenteric plexus
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achalasia: dx
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barium esophagogram (bird's peak); Manometry test to measure pressure in LES & reveal absence of peristalsis/ LES increased tone
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achalasia: tx
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myotomy of circular muscle over LES; channel blockers to relax LES; balloons to offer relief
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sources of infectious esophagitis
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herpes, CMV, candida; bacteria is rare
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implication of eosinophil for esophagitis
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allergy, asthma, infection
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GERD: ID, pathophysiology, sx
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failure of LES to prevent gastric regurgitation -> heartburn (pyrosis), inflammation; chest pain, which can radiate to neck
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GERD: risk factors
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hiatal hernia, obesity, pregnancy, smoking, alcohol, caffeine
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GERD: dx, tx
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endoscopy; PPI, histamine receptor antagonist, antacid
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Barret's esophagus: tx
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primary tx: surgical removal
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two types of GI motility
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segmental & peristaltic
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Importance of UES
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part of swallowing mechanism; prevents air entry (to maintain certain pressure level)
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innervation of stomach relaxation
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vagovagal reflex; swallowing -> relax
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ileogastric reflex
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distension in ileum -> decreases gastric motility
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role of atropine
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inhibits vagal stimulation of parietal cells
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change in parietal cell for activation
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tubulovesicles move to canaliculus
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cellular reaction w/in parietal cell
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H+/K+ ATPase on apical side; Na+/K+ ATPase on basolateral side; HCO3 to blood; Cl- to lumen; H+ and Cl- unite in lumen;
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how is G cell activated via nerve innervation
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via GRP from vagus n.
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phases of gastric acid secretion
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cephalic: afferent senses -> activate parietal & ECL (ACh), G cell (GRP), inhibit D cells;; gastric: food -> distension -> vagovagal reflex, partially digested protein -> G cells;; intestinal: AA in SI -> acid secretion
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gastroduodenal mucosal defense
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mucus-bicarbonate layer; microvascular system in submucosal layer -> defense/ repair, supply of nutrients/ oxygen, remove toxic; prostaglandins in mucosa: regulate release of mucus, bicarbonate, other; growth factors, proliferation
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etiology & mechanism: vomiting
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receptors in ear, overdistension of stomach/ duodenum, receptors in throat; reverse peristalsis via reflex by medullary centers
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etiology & tx for hypertrophic pyloric stenosis
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lack of inhibitory influences on pylorus or inadequate generation of NO; tumor, ulcer; surgical pyloromyotomy
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etiologies of acute gastritis
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NSAIDS, H. pylori, excessive alcohol consumption, radiation/ chemo
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gastroparesis: ID, sx, etiology, tx
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impaired/ delayed gastric emptying w/o evidence of obstruction; sx: satiety, nausea, vomiting of undigested/ partially digested food, bloating; etiology: diabetes, surgical, medical treatments; tx: small meals, low fat diets to inhibit CCK (CCK inhibits gastric movement)
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GUD vs DUD
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GUD: normal or low acid level; pain w/ meals; older paitent;; duodenal: acid level high, pain decrease w/ food, almost always H.pylori, "punched out" margins
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side effect of cimetidine
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increases gastric pH -> bacterial colonization -> pneumonia if inspirated into airway
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mechanism of H.pylori; dx; tx
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urease: produces ammonia from urea -> alkalize the surrounding; reduces somatostain, makes proteases & phospholipases to break down glycoprotein lipid complex of mucous gel; dx: urea breath test and serology tests for antibodies; tx: antibiotics, PPIs, H2 receptor blockers
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mechanism of autoimmune gastritis (reduced parietal)
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lower HCl -> higher gastrin and G cell (hyperplasia); pernicious anemia
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ZES: classical sx, tx
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increased gastrin secretion, PUD, diarrhea (due to inactive pancreatic enzymes due to high acidity); tx: whipple's, duodenotomy; PPIs, H2 blocker
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what pancreatic enzymes released?
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trypsin, chymotrypsin, carboxypeptidase, elastase, lipase, amylase, ribonuclease, deoxynuclease
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activation/ role of duodenal enzymes
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acidic chyme -> enterokinase -> trypsinogen to trypsin; CCK & vagal ACh stimulate acinar secretions; lipid presence in duodenum -> CCK release
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mechanism to protect pancreas from auto-digest
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acinar cells secrete trypsin inhibitor and ductal cells secrete HCO3- to keep the trypsin inactivated
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regulation of pancreatic HCO3- release
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response to secretin & ACh
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phases of pancreatic secretion
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cephalic: sensory-> ACh -> enzymes; gastric: distension -> ACh -> enzymes; intestinal: acid/ fat/ peptides, AA -> secretin/ CCK/ ACh -> enzymes + HCO3-
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cellular reaction w/in pancreatic duct cell
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Cl-HCO3- exchanger in apical side; CFTR release Cl to lumen in apical side; Na K ATPase exchanger on basolateral; H2O is split inside the cell; OH- used to make HCO3-, and H+ leave to blood
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etiology of acute pancreatitis
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GET SMASHED; gall stones, ethanol, trauma, steroids, mumps, autoimmune, scorpion stings, hyperlipidemia, ERCP, drugs
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pathogenesis of acute pancreatitis
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zymogens -> active form (esp. trypsinogen) in acinar cells -> autodigestion
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acute pancreatitis: sx, dx, tx
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epigastric pain -> radiate to back; nausea, anorexia, tachycardia, fever, peritonitis (leakage of pancreatic or bile fluids); dx: increased serum amylase & lipase, WBC; etiology would accopany liver enzymes & bilirubin; tx: depends on cause: EtOH cessation, gallbladder removal, etc.
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etiology, pathophys: chronic pancreatitis
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Mainly EtOH. Other (stone, trauma, CF, autoimmune); inflammation -> fibrosis & atrophy (irreversible);
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chronic pancreatitis: sx, dx, tx
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diabetes, steatorrhea, maldigestion, epigastric pain, weight loss; dx: serum, but more on imaging to reveal calcifications in pancreatic duct; tx: analgesics, surgical correction of duct obstruction, lipase supplement, EtOH cessation, diabetes management
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CF: pathophysiology
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CFTR defect -> decreased HCO3- & water secretion by ductal cells -> acinar secretions thicken -> obstruction -> maldigestion & steatorrhea
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secretion/ absorption of intestines
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net absorption of Na, Cl, water, K; secretion of HCO3-
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absorption of sodium in intestines
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sodium-glucose (SGLT1) & sodium-AA transport after meal in proximal; when bicarbonate in lumen -> sodium-proton exchange; ENaC: enhanced by aldosterone (mainly in colon), inhibited by CFTR
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absorption of chloride in intestins
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driven by sodium absorption, voltage-dependent chloride absorption; chloride-bicarbonate exchanger;
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absorption/ secretion of potassium in intestines
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proximal segments (SI) absorb passively, distine segments (LI) secrete passively (paracellular) & actively (transcellular);
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mechanism of cholera & VIP
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activates AC -> increase cAMP -> permanent GTP bound state -> opens CFTR to drive chloride out -> diarrhea
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regulation of intestinal ion transport
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aldosterone: stiumlate electrogenic sodium absorption in colon; cAMP, cGMP, calcium -> enhance anion secretion, inhibit Na Cl absorption; mineralocorticoids, glucocorticoids, somatostatin -> enhance absorption; antigen activates mast cells -> secrete fluid
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basic digestion/ absorption of carb
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salivary & pancreatic alpha amylase, SI brushborder disaccharides; glucose & galactose via SGLT1 (2ndarily active); fructose via GLUT5 (passive); GLUT2 on basolateral
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basic digestion/ absorption of protein
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gastric & pancreatic proteases, some by brush border enzymes; AA & peptides absorbed via PepT1 (due to sodium-proton exchanger) -> further digested inside enterocyte -> shipped out passively
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basic digestion/ absorption of fat
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lingual, gastric, pancreatic lipase; pancreatic lipase (secreted as active) w/ colipase, phospholipidase A2 -> enters as micelle (short, medium FAs enter paracellularly) -> form chylomicrons inside -> lymphatics
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site of nutrient absorption
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calcium, iron, folate: mostly duodenum; bile acids: mostly in ileum; carbs, protiens, lipids: small intestine, decreasingly as it progresses;
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neonatal protein absorption
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whole protein apical pinocytosis -> passive immunity from mother
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pathophysiology of Hartnup's disease
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tryptophan malabsorption; tryptophan appears in normal
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pathophysiology of cystinuria
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transporter for the dibasic amino acids cystine, lysine, arginine, and ornithine is absent in both the small intestine and the kidney
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pathophysiology of abetalipoproteinmia
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mutation in protein that catalyze formation of chylomicrons; steatorrhea
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dx for steatorrhea
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test for TAG or FFA in stool (qualitative); fecal fat from 72 hr -> titrate for fecal lipid (quantitative)
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Describe schilling's test
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To determine whether it's ileum, B12, or IF's problem; labeled B12 & collect it in urine to measure progress
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calcium absorption
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regulated by vitamin D; active transport (transcellular) in duodenum; passive (paracellular) in other areas of SI
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Magnesium absorption & fn
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active in ileum; passive in duo/jeju; cofator for neurotransmission & muscular contractions; proper secretion of parathyroid hormone
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iron absorption
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only in duodenum; ferric to ferrous in apical; ferous to ferric in basolateral; carried by transferrin in blood
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pathophysiology, sx, dx, tx of hemochromatosis
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too much iron accumulation in organs; liver (cirrhosis), pancreas (diabetes), arthritis, bronze pigmentation; not as much to women (menstrual flow out); dx: high serum iron, transferrin, ferritin, liver bx; tx: phlebotomy (blood removal)
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celiac: pathophysiology; sx; dx; tx
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autoimmune response to alpha-gliadin (resistant to degradation); absence of villi, malabsorption, diarrhea, joint pain, anemia,; dx: hypocalcemia, hypoalbuminemia, diagnostic antibodies (IgG antigliadin, IgA antigliadin, IgA tissue transglutaminase, IgA endomysial) , duodenal bx, confirmation of improvement after gluten-free
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gastrocolic reflex
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urge to defacate after gastric distention
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bacterial overgrowth: pathophysiology, dx, tx
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impaired motility, obstruction, fistula -> stasis -> overgrowth -> competition for nutrients, impaired micelle formation, diminished brush border enzymes, lactic acidosis; dx: hydrogen breath test after oral glucose take; tx: correction of anatomical abnormality & antibiotics
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Hirschsprung's disase: etiology, pathophysiology, sx, dx, tx
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neural crest cells' no caudal migration -> partial absence of ganglion cells in plexuses, no interstitial cells of cajal -> internal anal sphincter not relax, no coordinated peristaltic contractions -> chronic constipation early; dx: IHC stain to ID ganglion cells; tx: remove segment missing plexuses, connect gap
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Meckel's diverticulum: ID, pathophys, dx
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diverticulum in ileum of gastric or pancreatic tissue; failed involution (closure) of vitelline duct (w7) -> palpable abdominal mass, painless rectal bleeding; dx, tx: barium enema
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Zenker's diverticulum: ID
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false diverticulum at pharyngoesophageal junction
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mechanisms of intestinal obstruction
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hernia, adhesion, volvulus, intussusception (telescoping)
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diarrhea: dx
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osmotic: stops w/ fasting, increased osmotic gap in stool, lose more water than electrolytes, no fecal fat; secretory: little to no structural damage, no blood, pus, fat in stool; persist w/ fasting, isotonic stool
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C. Difficile mechanism
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after normal flora killed by antibiotics, C. Difficile becomes predominant -> release proteins A & B -> binds and cause epithelial cells to slough off -> mucosal ulceration & pseudomembranes
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ID: colonic diverticulosis
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most common cause for hematochezia; susceptible to rupture, bleeding; most are in left colon, but right sided more likely to bleed
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ulcerative colitis - different from crohn's
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only colon & rectum, mucosa & submucosa; increased risk for colon cancer; continuous ulcer, no stricture or granuloma
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crohn's - different from UC
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anywhere in GI, but ileum & colon (not rectum) likely, not continuous, not as risky for cancer, transmural, fistula, fat/ vitamin malabsorption, stricture
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inflammatory bowel disease (IDS): pathophysiology, sx, tx
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host interaction & intestinal microbiota, epithelial dysfunction & mucosal immune response; sx: diarrhea, abdominal pain, WBC count, joint pain; tx: 5-ASA, corticosteroids, antibiotics, probiotics, colectomy curable for U.C., not for Crohn's
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prednisone
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corticosteroids
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ID: McBurney's point, Rovsing's sign, psoas sign, obturator sign; dx, and other possible ddx
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mcburney's: 2/3 distance from umbilicus to right ASIS; rovsing's: push left, pain right; psoas: iliopsoas muscle movement (retroperitoneal) -> retrocecal orientation; obturator: in contact w/ obturator internus; dx: CT; ddx: ectopic pregnancy & diverticulitis
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name different liver cells & function
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stellate cells: contain lipid droplets, produce type 1, 3 collagen; kupffer cells: macrophages of liver; pit cells: natural killer cell activity; cholangiocytes lining bile duct
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different zones and relation to nearby structures
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zone 1: closest to portal, most oxygenated, affected first by viral hep; zone 3: next to central venule, susceptible to hypoxia, ischemia, has p450 -> sensitive to toxic injury of acetominophen & EtOH
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liver functions
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bile, plasma protein, fat soluble vitamins production; AA deamination; carb homeostasis, lipid metabolism, iron homeostasis, detox, conversion of thyroid hormones, vitamin D activation, insulin & glucagon degradation
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AST, ALT, ALP,
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AST: many tissues like RBC, skeletal m., cardiac m.; ALT: more spc. To liver; ALP: enzyme in cells lining biliary tracts of liver
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circulation of bilirubin metabolism
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heme -> UCB (not soluble) -> CB in liver (soluble) -> exit as bile -> via enteric bacteria become UCB -> UBG (colorless) -> reabsorbed or excreted as stercobilin in feces or via kidney as urobilin (yellow)
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significance of unconjugated bilirubin
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increase in heme production; liver function -> not as capable of conjugating
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significance of conjugated bilirubin
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obstruction -> CB not being sent to intestine; liver cell necrosis
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complications of liver failure
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hepatic encephalopathy: asso. w/ elevated ammonia level, brain edema, asterixis, confusion; hepatorenal syndrome: renal failure w/ no functional causes, elveated creatinine & urea; hepatopulmonary syndrome: hypoxemia, decreased oxygen saturation, increased dyspnea
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ID: cirrhosis
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irreversible fibrosis leading to portal hypertension; parenchymal nodule formation or regenerating hepatocytes surrounded by fibrosis; disrpution of entire liver
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sx of portal hypertension
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hepatic encephalopathy, skin spider angiomata, esophageal varices, splenomegaly, periumbilical caput medusae, ascites, hemorrhoids
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pathophysiology of wilson's disease; sx
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mutation -> copper not excreted in bile as much -> decreased ceruloplasmin -> Cu deposits in many tissues, such as liver, brain, eye; asterixis, basal ganglia degenration, corneal copper, cirrhosis, dementia
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function of alpha-antitrypsion
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inhibits proteases (elasttase, trypsin) & neutrophil elastase;
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what is bad comorbidity of ALD?
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chronic infection of hep C
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disulfram
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inhibits acetaldehyde dehydrogenase -> bad sx whenever drink alcohol
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naltrexone
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opioid receptor antagonist -> reduces cravings for EtOH
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cirrhosis's role in creating portal hypertension
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stellate cells -> type 1, 3 collagen -> fibrosis -> loss of fenestrations in sinusoids -> change in pressure
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MELD calculation
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creatinine, bilirubin, INR (prothrombin time)
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causes of hepatitis
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drug allergy, inflammation due to toxins, viruses; alcohol,
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HAV: transmission, tendency, dx
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via water, food; blood transmission rare; mild, asymptomatic, or acute, not chronic; dx: IgG -> already exposed/ vaccinated, IgM antibodies & fecal HAV shedding -> active
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HBV: dx
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idea: look for HBsAg or anti-HBcAg (IgG), antiHbs; HBeAg starts later & ends earlier; a
cute: HBsAg, HBeAg, IgM, window phase: just IgM; ; chronic: HBsAg, IgG, HBeAg healthy chronic: HBsAg, IgG, but not HBeAg cured: anti-HBcAg (IgG), anti-HBs immunized: anti-HBs |
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HBV: transmission, tx
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parenteral, sexual, perinatal; interferon alpha-2a
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ribavirin
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guanosine analog -> inhibits viral mRNA; for HepC
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HCV: dx
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rtPCR for HCV RNA; HCV-RNA & anti-HCV; anti-HCV means infection or recovery, not protective antibody;
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HDV: transmission, dx
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Parenteral transmission; IgM, IgG, HDV RNA, HDAg
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superinfection of hep V
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HBV + HDV; carrier of HBV exposed to HDV -> superinfection; elimination of HBV -> elimination of HDV
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HEV: transmission, tendency, dx
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fecall-oral; not chronic; dx: PCR for RNA, IgM, IgG
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autoimmune hepatitis: dx, tx
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dx: anti-nuclear, anti-smooth muscle, anti-actin; tx: immunosuppresants
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acetaminophen-induced liver damage: pathophys
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metabolism via cytc p450 -> reactive compound -> ROS; worsen by ethanol -> less degradation of cytc 450
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tx for encephalopathy
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lactulose: sugar only digested by colonic bacteria -> lower pH -> protonation of ammonia -> ammonium excertion; low protein diet to reduce ammonia production
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cause of ascites
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decreased degradation of aldosterone by liver -> more sodium, water retension
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EtOH metabolism; pathophysiology
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EtOH -> acetaldehyde (via alcohol dehydrogenase) -> acetate (via acetaldehyde dehydrogenase); increases NADH/NAD+ ratio; pyruvate -> lactate, OAA -> malate; no gluconeogensis, more FA synthesis; hypoglycemia, hepatic fatty change
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fomepizole
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inhibits alcohol dehydrogenase
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role of estrogen in liver pathology
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estrogen not broken down as much; gynecomastia; estrogen -> increased vascularity -> palmar erythemia, spider angiomas, portal hypertension
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gallbladder: electrolyte control
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concentrate bile, sodium-proton exchanger to acidify bile -> calcium salt precipitation not as likely
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regulation of bile secretion
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secretin: stimulates bicarb release into bile ducts; CCK & ACh stimulate release; somatostatin inhibits bicarb release into bile ducts
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two types of cholelithiasis; causes; dx
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cholesterol stones: not enough bile acids to keep cholesterol (estrogen, OCT, obesity) in miccelles, + hypomotility; unconjugated bilirubin (pigment stones): bacterial infection of biliary tract -> deconjugate bilirubin -> less soluble, complexes w/ calcium -> black stone; Murphy's sign, US
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causes of obesity; risk factors
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diet, basal metabolism, hormones, cytokines, adipokines, sleep, gut flora, activity; family history, gender, ethnicity, childhood obesity, lower socioeconomic status, sedentary lifestyle,
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BMI
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kg/ m^2
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metabolic syndrome: criteria
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abdominal obesity, elevated TAG, low HDL, hypertension, high fasting glucose;
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changes in gastric bypass
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gastric pouch smaller; duodenum and a lot of jejunum bypassed since food exits via outlet/ not pyloric sphincter; pancreatic and billiary secretions to the distal ileum; ghrelin lower; PYY higher; some malabsorption
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mechanisms of complications of gastric bypass
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rapid filling of hyperosmotic chyme -> diarrhea, emesis, diarrhea; reduced lipolytic enzymes -> steatorrhea; vitamin D defiency (fat soluble), iron, calcium, thiamine; most important: b12 & Fe; dumping syndrome; mild protein defiency; lactose intolerance
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lifestyle for patients w/ gastric bypass
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avoidance of simple & refined carb; eat small frequent meals;
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body's adaptation after gastric bypass
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villi hypertrophy (not plasia); management of nitrogen excretion; ghrelin suppressed
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gut -> CNS control
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paracrine/ endocrine signal -> ileum -> CNS (appetite/ satiety), ex. Leptin from adipocytes -> satiety (hypothalamus); stomach, intestine -> ghrelin -> hunger (hypothalamus); PYY (peptide YY) from L cells distal bowel, colon -> decrease ghrelin level; L cells of distal bowel -> GLP (glucagon like peptide) -> increase insulin secretion/ insulin sensitivity
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name plasma lipoproteins & their density; their source
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chylomicrons (lowest density, dietary); VLDL (liver), LDL, HDL
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HDL's mechanism
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pick up cholesterol & phospholipids via ABCA-1; LCAT inside HDL esterifies cholesterol; cholesterol taken directly by SR-B1 (scavenger receptor) to liver, or to chylomicrons & VLDL via cholesterol ester transfer protein (CETP)
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Tangier disease: cause
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defect in ABCA-1; cant take cholsterol/ phospholipids from periphery to HDL
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mechanism of atherosclerosis
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too much cholesterol in tissues -> don't take up -> longer duration & more concentration -> oxidized LDL -> macrophages take cholesterol esters -> foam cells
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ezetimibe
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blocks cholesterol uptake from gut by inhibitting SI transporter -> lower LDL
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niacin
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increases HDL
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mechanism of cholestyramine, colestipol
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bile resins; binds to bile acids in SI -> prevent absorption -> more LDL uptake by liver to make bile acid -> less LDL
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role of gastric acid
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denature protein, kill bacteria, activate pepsin
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role of prostaglandin
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stimulate mucus, bicarb secretion; increased mucosal blood flow; limit diffusion of acid to epithelium
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common lab tests to check liver function
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serum albumin & prothrombin time; half life of albumin: 20 days; prothrombin - 5~7 days of half life; bilirubin
|
|
|
which reactions occur in mitochondria?
|
beta oxidation, TCA, ox phos, heme synthesis, urea cycle, gluconeogenesis
|
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|
which reactions occur in cytoplasm
|
glycolysis, FA synthesis, PPP shunt, protein synthesis, steroid synthesis
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|
rate determining enzyme for glycolysis?
|
PFK-1
|
|
|
rate determining enzyme for gluconeogenesis?
|
F1,6 bisphosphatase
|
|
|
rate determining enzyme for TCA cycle
|
isocitrate dehydrogenase
|
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|
rate determining enzyme for glycogen synthesis?
|
glycogen synthase
|
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|
rate determining enzyme for glycogenolysis
|
glycogen phosporylase
|
|
|
rate determining enzyme for PPP shunt
|
glucose6phosphate dehydrogenase (G6PD)
|
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|
rate determining enzyme for de novo pyrimidine synthesis; regulation
|
carbamoyl phosphate synthetase II (CPS2); activated by PRPP, inhibited by UTP
|
|
|
rate determining enzyme for de novo purine synthesis
|
glutamine-PRPP amidotransferase
|
|
|
rate determining enzyme for urea cycle; regulation
|
carbamoyl phosphate synthetase I (CPS1); activated by NAG (N-acetyl-glutamate), which is activated by arginine.
|
|
|
rate determining enzyme for FA synthesis
|
acetyl-CoA carboxylase (ACC)
|
|
|
rate determining enzyme for FA oxidation; regulation
|
carnithine acyltransferase I or CPT1; allosterically inhibited by malonyl-coA, which is product of ACC
|
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|
rate determining enzyme for ketogenesis
|
HMG-CoA synthase
|
|
|
rate determining enzyme for cholesterol synthesis; regulation
|
HMG-CoA reductase; requires 2 NADPH molecules; release CoA (so irreversible); inhibited by cholesterol; insulin & thyroxine up-regulate it; glucagon, glucocorticoid downregulate; targetted by statin drugs
|
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|
covalent regulation of glycogen synthesis
|
insulin activates phosphodiesterase activates glycogen synthase
|
|
|
covalent regulation of glycogen break down
|
glucagon/ epinephrine, via PKA, phosphorylates pohsphorylase kinase, which phosphorylates to activate glycogen phosphorylase
|
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|
allosteric regulation to encourage glycogen synthesis
|
G6P activates glycogen synthase ; in liver, glucose inhibits glycogen phosphorylase; ATP inhibits glycogen phosphorylase. (think in terms of muscle energy)
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|
allosteric regulation of glycogen break down
|
in muscle, AMP activates glycogen phosphorylase; calcium binds to calmodulin and activates phosphorylase kinase w/o PKA phosphorylation; in liver, calcium activates PKC, which phosphorylates to inactivates glycogen synthase
|
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|
another name for vitamin C. Why is it needed for collagen synthesis?
|
ascorbic acid; hydroxylates proline & lysine; needed for hydrogen bond;
|
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|
what is produced from PPP? Regulation of PPP.
|
NADPH produced; thus NADP+ needed. NADPH inhibits; insulin upregulates G6PD; irreversible.
|
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|
Important role of NADPH from PPP for RBCs
|
used by glutathione reductase; anti-oxidant & DNA synthesis
|
|
|
Explain G6P dehydrogenase deficiency
|
No PPP; PPP only source of NADPH in RBC -> hemolytic anemia
|
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|
what does oxidative portion of PPP produces? What can it become?
|
ribulose 5-phosphate; when NADPH high, convert to ribose 5-phospohate for nucleotide ; when NADPH low, fructose 6P or G3P for glycolysis.
|
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|
when PPP product converts to glycolysis product, what's produced; what enzyme and cofactor?
|
ribulose 5-phosphate to F6P and G3P. Transketolase and transaldolase; TPP needed. (thiamine derivative)
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|
citrate's role in allosteric regulation
|
inhibits citrate synthase; inhibits PFK1, activates acetyl-CoA carboxylase; citrate synthase inhibited by ATP
|
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|
regulation of isocitrate dehydrogenase
|
its work = irreversible; activated by ADP & ca2+; inhibited by NADH, ATP; requires NAD+
|
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|
regulation of alpha-ketoglutarate dehydrogenase
|
requires TPP, lipoid acid, FAD, NAD+, CoA; inhibited by NADH, ATP, succinyl CoA; activated by Ca2+
|
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|
regulation of PDH. Distinguish allosteric & covalent regulation. What other cofactors required?
|
covalent: via PDH kinase, inhibted by ATP, acetyl CoA, NADH, activated by pyruvate; covalent: via PDH phosphatase, activated by Ca2+, Mg2+, ADP, NAD+; allosteric: acetyl coA & NADH inhibitors; req TPP, lipoic acid, coA, FAD, NAD+
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|
what are irreversible enzymes for glycolysis?
|
GK/ HK; PFK-1; PK
|
|
|
gluconeogenesis, how to go from pyruvate to PEP? Regulation?
|
pyruvate carboxylase for pyruvate -> OAA; biotin, ATP, CO2 needed, activated by acetyl CoA; malate dehydrogenase for OAA -> malate, NADH needed; shuttle, back to OAA, NADH produced; PEPCK for OAA -> PEP, GTP required
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|
gluconeogenesis, how to go from F1,6BP to F6P? Regulation?
|
F1,6 Biphosphatase; inhibited by AMP and F-2, 6-BP; activated by ATP; glucagon -> PKA -> phosphorylate PFK2/FBP2 (bifunctional); no glucagon -> not phosphorylated PKF2/FBP2;
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|
gluconeogenesis, how to go from G6P to glucose? Regulation?
|
*** G6Phosphatase; compartmentalizaiton in ER.
|
|
|
defect in G-6-Phosphatase. Impact.
|
glycogenolysis and gluconeogenesis inhibited. -> severe hypoglycemia.
|
|
|
glucagon's stimulation of gluconeogenesis
|
allosteric: increase F-2,6phosphatase -> less F2,6BP; covalent: phosphorylate to inactivate PK; enzyme: increases txn of PEPCK gene
|
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|
AMP's role in gluconeogenesis
|
drives glycolysis: inhibits fructose 1,6-biphosphatase, activates PFK-1
|
|
|
futile cycle control for gluconeogenesis, how is PK portion controlled?
|
enzyme synthesis for both: glucagon; alanine & ATP also inhibit PK
|
|
|
futile cycle control for gluconeogenesis, how is PFK-1 portion controlled?
|
allosteric for both: F-2,6-BP (controlled by glucagon, insulin)/ AMP/ ATP
|
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|
futile cycle control for gluconeogenesis, how is G6Pase portion controlled?
|
enzyme synthesis for both: insulin/ glucagon; compartmentalization
|
|
|
How is PFK-1 regulated?
|
activated by AMP, F-2,6-BP; inhibited by citrate, ATP, low pH; Mg2+ req. glucagon/ insulin covalently regulates F-2,6-BP kinase/ase & PFK1
|
|
|
How is PK regulated?
|
PK inhibited by alanine, glucagon, ATP; activated by F-1,6-BP; activated by insulin; Mg 2+ req.
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|
|
How is G6Pase regulated?
|
** G6Pase is compartmentalized in ER
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|
two NADH shuttle for glycolysis to ETC, what organs, how many ATPs?
|
basically reduce first in cytoplasm, then oxidize in mitochondria; Called "G3P shuttle"; DHAP <-> G3P (you use NADH to make glycerol); NADH -> FADH2; 1.5 ATP/FADH2; brain, muscle;; called "malate-aspartate shuttle" malate <-> OAA; NADH; 2.5 ATP/ NADH2; heart, liver
|
|
|
how is HK and GK regulated?
|
HK inhibited by G6P. GK inhibited by F6P, stimulated by glucose; Mg2+ required.
|
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|
How is PFK-2 regulated?
|
PFK-2/FBP-2 is bifunctional enzyme; insulin -> activate PFK-2 via dephosphorylation; glucagon/epinephrine activates F-2,6-biphosphotase
|
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|
what happens when PK deficient?
|
hemolytic anemia
|
|
|
What does CPS2 stand for, what pathway, and regulation?
|
**carbamoyl phosphate synthetase II; de novo pyrimidine synthesis; activated by ATP, PRPP; inhibited by
|
|
|
In de novo purine synthesis, how is balance of nucleotide bases shown?
|
AMP synthesis requires GTP; GMP synthesis requires ATP; AMP, GMP inhibit their own synthesis from IMP; first step inhibited by GMP, IMP, AMP collectively, so if one of them in access, no go
|
|
|
what are the enzymes of purine salvage? Their regulation?
|
HGPRT and APRT; HGPRT inhibited by IMP, GMP; APRT inhibited by AMP;
|
|
|
With ALT, what are substrate and product?
|
alanine, pyruvate
|
|
|
With AST, what are substrate and product?
|
OAA, aspartate
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|
from purine nucleotide cycle, ammonia and TCA intermediate can be generated. What stage and how?
|
prolonged fasting; ribose-5P + aspartate -> fumarate + ammonia
|
|
|
How are vitamin B1 and B12 used together in function?
|
N5-methyl THF -> THF only done with B12. Then homocysteine -> methionine.
|
|
|
fed state, what activates glycogen synthesis
|
G6P activates glycogen synthase
|
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|
fed state, what activates PPP
|
elavated G6P increases PPP activity; FA synthesis -> req. NADPH
|
|
|
fed state, what activates glycolysis
|
insulin -> glycolysis; GK (liver) has high Km, receives lots of glucose, let them in (GLUT2);
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|
fed state, what activates TCA
|
pyruvate activates PDH -> lots of acetyl CoA; AA -> lots of TCA intermediates
|
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|
fed state, what activates FA syn
|
high acetyl CoA, NADPH -> activated ACC -> FA synthesis
|
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|
fed state, why no gluconeogenesis
|
*low acetyl CoA inactivates pyruvate carboxylase
|
|
|
what happens in fed state in liver
|
protein synthesis, lipid synthesis, AA degredation for E production, increased glycolysis & TCA, increased PPP, increased glycogen synthesis
|
|
|
what happens in fed state in muscle?
|
glucose absorbed -> glycogen & TCA; AA absorbed -> protein
|
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|
what happens in fed state in adipocyte?
|
glucose -> TCA, acetyl coA -> TAG; chylomicrons (from gut) -> TAG; VLDL (liver) -> TAG
|
|
|
what metabolic hormone receptors for muscle?
|
insulin and epinephrine; no glucagon; muscle doesn't synthesize glucose
|
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|
during fasting, proteins -> AA. Explain three locations where AA's are converted to enter different pathways.
|
alanine -> pyruvate -> gluconeogenesis in liver; glutamine -> glutamate -> alpha-ketoglutarate & ammonia in kidney; ammonia combines w/ ketonic hydrogen to make ammonium (buffer for acidity); gut: absorb glutamine -> metabolize to alanine -> liver
|
|
|
time line of glucose homeostasis during fasting
|
first ~4 hrs: exogenous glucose, all tissues use glucose; 4~16 hrs: from glycogen, then hepatic gluconeogenesis; glucose used by all, but muscle & adipocytes use less; 16~day 2: more hepatic gluconeogenesis than glycogen, liver doesn't use glucose; adipocytes & muscle use even less glucose; d 2~24: hepatic and renal gluconeogensis, glucose & ketone bodies used by brain, rbcs, renal medulla, small amt by muscle; d24 and on: hepatic & renal gluconeogen, brain, rbcs, renal medulla, more ketone bodies than glucose
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|
|
from glutamine, how is it introduced to TCA, and in what organ?
|
in kidney; glutamine -> deaminated to glutamate -> further deaminated & dehydrogenizd (NADH) to alpha-ketoglutarate
|
|
|
PKA activity; where does it happen w/ what hormones? Which pathways does it affect?
|
glucagon & epinephrine actvates PKA in the liver (no glucagon affect in muscle); PKA increases activity of glycogenolysis & gluconeogenesis; decreases activity of glycolysis & lipogenesis
|
|
|
fasting state, what happens in liver
|
glycogenolysis; gluconeogenesis; beta oxidation from FFA from adipocyte; AA -> pyruvate (gluconeogensis & acetyl coA) & TCA; acetyl coA -> ketone
|
|
|
fasting state, what happens in adipocyte
|
TAG -> FFA + glycerol; FFA -> TCA in the cell, and ship to liver; glycerol ship to liver
|
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|
fasting state, what happens in muscle
|
FFA from adipocyte -> TCA; ketone bodies from liver -> TCA; protein -> ship AA to liver
|
|
|
what hormones during fasting?
|
cortisol, epinephrine, glucagon, little bit of insulin
|
|
|
How many energy products per TCA cycle? (from one acetyl coA)
|
3x NADH, 1xFADH2, 1xGTP
|
|
|
what enzyme is embedded in TCA cycle? What does it do?
|
succinate dehydrogenase; complex 2 in ETC; oxidizes FADH2
|
|
|
which enzymes produce what energy products in TCA cylce? Name the substrate & product of the enzyme
|
isocitrate dehydrogenase creates NADH (isocitrate -> oxalosuccinate); alpha-ketoglutarate dehydrogenase creates NADH (alpha-ketoglutarate -> succinyl coA); succinyl CoA synthase creates GTP (succinyl CoA -> succinate); succinate dehydrogenase creates FADH2 (succinate -> fumarate); malate dehydrogenase creates NADH (L-malate -> oxaloacetate)
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|
|
talk about anaplerosis, open & closed cycle; in which tissues?
|
creation of TCA cycle itnermediates; high in liver & muscle where cycle is open; low in most (closed)
|
|
|
examples of anaplerosis; enzyme, what organ, regulation
|
pyruvate carboxylase for pyruvate -> OAA; most tissues; biotin, ATP, CO2 needed, activated by acetyl CoA;; glutamate dehydrogenase: glutamate -> alpha-ketoglutarate in liver; ribose-5P + aspartate -> fumarate + ammonia, part of pure purine synthesis;; aspartate -> OAA via AST;
|
|
|
which two AA's are ketogenic?
|
leucine & lysine
|
|
|
what happens when PDH deficient? Treatment?
|
excess pyruvate (to restore NAD+) -> lactic acid; congenital lactic acidosis; neurological defects; tx: high fat foods of ketogenic nutrients to enter TCA w/o using PDH, oral citrate supplement;
|
|
|
what other cuase of PDH deficiency besides congenital?
|
TPP deficiency in alcoholics
|
|
|
There are two types of GLUT we covered. Which GLUT are there and in which organs?
|
GLUT4 - major transporter in skeletal m.; GLUT2 - liver, pancreas
|
|
|
what's special about RBC?
|
converts 1,3BPG to 2,3BPG; fast turnover; very dependent on glycolysis & PPP
|
|
|
compare & contrast GK & HK
|
HK has lower Km and Vmax. Non-cooperative. Inhibited by G6P; GK has higher Km & Vmax (to prevent hyperglycemia). Activated by glucose, inhibited by F6P. Insulin stimulates gene expression of GK
|
|
|
what can pyruvate become?
|
lactate, acetyl coA, OAA, alanine
|
|
|
gluconeogenesis: sources of carbon in liver
|
alanine, glutamine most common; glycerol, lactate
|
|
|
what pathways does fructose go into?
|
non-insulin dependent entry; enter glycolysis as DHAP or G3P. Also can go to TAG synthesis as glycerol
|
|
|
what pathology of fructose can occur?
|
essential fructosuria: fructokinase problem; hereditary fructose intolerance: aldolase problem (accumulate as F1P); both: fructose in blood/ urine; low ATP -> inhibition of gluconeogensis/ glycogenolysis -> hypoglycemia; tx: remove fructose, sucrose, sorbitol from diet
|
|
|
what pathways does galactose go into?
|
non-insulin dependent entry; from UDP-galactose, can become lactose, UDP-glucose.
|
|
|
what pathology of galactose?
|
classic galactosemia: absence of galactose-1-P uridyltransferase -> can't become UDP-galactose; galactokinase deficiency: can't become galactose-1-P; both: too much galactose -> become galactitol: galactose appear in blood/ urine; galacitol in eye (cataract), failure to thrive; tx: no galactose & lactose in diet
|
|
|
general construction of lipoprotein
|
core TAG, cholesterol esters; shell of apoproteins, phospholipids, cholesterol
|
|
|
essential fatty acids. Pathology for deficiency.
|
linoleic & alpha-linolenic acid; scaly dermatitis.
|
|
|
destination of TAG's constituents during fasting: organs, pathways
|
beta-oxidation & TCA from nearly all tissues; ketone bodies in liver
|
|
|
what organ, part of the cell does fatty acid synthesis occur? What are required to run this?
|
in liver, mammary glands, adipocytes; cytosol; acetyl coA, ATP, NADPH req
|
|
|
transport of acetyl coA to cytosol for fatty acid synthesis. Name enzyme used. What happens to the other product? Its significance?
|
acetyl coA + OAA -> citrate +coA ----> citrate + ATP + coA -> acetyl coA + OAA; via ATP citrate lyase; OAA (from cytosol) converts to malate then to pyruvate, pyruvate enters mitochondria; malate -> pyruvate creates NADPH.
|
|
|
rate limitting enzyme for fatty acid synthesis; substrate/ product; regulation; what diabetes drug interferes with this pathway?
|
acetyl coA carboxylase (ACC): acetyl coA -> malonyl coA; rate limiting; activated by citrate; inactivated by palmitoyl coA (end product) & AMP kinase (muscle) (phosphorylates ACC); glucagon & epinephrine activates PKA which activates AMPK; opposite for insulin; metformin also activates AMPK.; AMP also inactivates ACC allosterically. (low E -> should go TCA -> ETC); biotin & ATP required.
|
|
|
What is the key enzyme for fatty acid synthesis; one after ACC. Regulation. End product.
|
fatty acid synthase (FAS). Requires NADPH, which comes from PPP & malate-> pyruvate conversion. End product: palmitate..
|
|
|
what are substrates and products of ketone body synthesis? How is it carried in blood? Anything to note about urine test?
|
substrates: acetyl coA, ketogenic AA's, fatty acyl coA (beta oxidation); products: acetone (deadend) + 3-hydroxybutyrate; soluble in blood; urine test doesn't detect beta-hydroxybutyrate.
|
|
|
which organs use ketone body? Why not liver?
|
heart, muscle, brain; liver missing enzyme (3-ketoacyl coA transferase)
|
|
|
ketone synthesis' rate limiting enzyme. Its substrate/ product.
|
HMG coA synthase; substrate: acetoaccetyl coA, product: HMG coA.
|
|
|
how is FFA transported into mitochondria for beta ox? Which proteins are important? Regulation
|
long FFA: carnithine transport; short, mediam: no carrier; carnitine palmitoyl-transferase I (CPT1) in outer mitochondrial membrane; carnitine palmitoyl transferase II (CPT2) in inner mitochondrial membrane; basic idea: CPT1 removes coA from fatty acyl, adds carnitine; CPT2 removes carnithine and adds coA to fatty acyl; CPT aka CAT (carnitine acyltransferase); malonyl coA inhibits CPT1 (thus rate limiting)
|
|
|
explain beta ox once inside mitochondria
|
fatty acyl coA -> fatty acyl coA (2 carbons shorter) + acetyl coA; NADH and FADH2 produced. ; last fatty acid (3C long) (propionyl coA) metabolized to succinyl coA (biotin, vitamin b12 req)
|
|
|
what enzyme for TAG breakdown? Regulation?
|
lipase; covalent regulation: activation via adrenaline/ glucagon, inactivation by insulin
|
|
|
one pathology for beta ox
|
medium-chain fatty acyl coA dehydrogenase deficiency; can't oxidize these FFAs. Dx: increased in urine; hypoglycemia (these tissues take in more glucose); tx: avoid fasting, carnitine suplpementation
|
|
|
role of branching in glycogen; what linkage is considered branching?
|
alpha 1->6; branching makes glycogen more soluble; accelerates rate of glycogen synthesis.
|
|
|
what is limiting enzyme for glycogen synthesis; what linkage created? What is substrate
|
glycogen synthase; creates alpha(1->4) linkage; substrate: UDP-glucose
|
|
|
how are alpha(1-6) and alpha(1-4) bonds lyased in glycogen? Which is rate limiting?
|
glycogen phosphorylase (rate limiting) breaks alpha(1->4) linkage; 4:4 transferase removes outer three of four residues for alpha(1-6) branch; 1:6 glucosidase removes the last one on alpha(1-6) branch.
|
|
|
name one glycogen storage disorder and mechanism. Treatment.
|
mcardle's disease: glycogen phosphorylase deficient, too much glycogen, diminished exercise tolerance. Tx: sucrose supplementation, aerobic exercise (non-glucose TCA cycle) w/ creatine & vitamin B6.
|
|
|
branched AA's
|
leucine, isoleucine, valine.
|
|
|
10 essential AA's; characteristic?
|
PVT TIM HALL; phenylalanine, valine, tryptophan, threonine, isoleucine, methionine, histidine, arginine, leucine, lysine; no acidic; all branched, basic AAs included.
|
|
|
what is coenzyme for aminotransferase?
|
pyridoxal phosphate (vitamin b6 derivative)
|
|
|
what two AA's not transaminated?
|
lysine, threonine
|
|
|
how is redox and transamination related?
|
deamination is oxidative, while amination is reductive; NADPH/NADP+ or NADH/NAD+ used
|
|
|
explain transport of ammonia. From where to where? What happens once arrives in the destination?
|
glutamine: non-toxic transport, from anywhere to liver, produces glutamate; forms alanine from muscle, shipped to liver, transaminated back to pyruvate. Ammonia then turns to urea.
|
|
|
what's special about branched chain AA? Connection to pathology and vitamin?
|
different enzymes. Oxidative decarboxylation via branched-chain alpha-ketoacid dehydrogenase (BKAD); require TPP. Subsequent step also requires biotin and vitamin b12. Defect in BKAD -> maple syrup urine disease; accumulation of branched alpha-ketoacid in urine -> sweet odor -> CNS defects
|
|
|
two one-carbon carriers; their sigficance
|
THF & SAM; THF derived from folic acid. Folic acid -> THF requires NADPH; conversion from N5-CH3-THF to THF requires b12; THF then aids in methionine production. THF also produced from bacteria; different DHFR enzyme, so inhibitor of bacteria -> antibiotics, inhibitor of human -> chemotherapy; SAM synthesized from ATP & methionine.
|
|
|
list some products from AA metabolism
|
catecholamines (from tyrosine, which is from phenylalanine); NO from arginine; histamine from histidine
|
|
|
Name most common error in AA metabolism & its mechanism
|
phenylketonuria (PKU); defect in conversion phenylalanine -> tyrosine; build up of phenylalanine, deficiency of tyrosine; urine: musty odor, elevated phenylalanine level, melanin deficiency (tyrosine) -> hypopigmentation.; tx: restrict phenylalanine, replace tyrosine.
|
|
|
what's an important pathology concerning pyrimidine synthesis? Its significance?
|
orotic aciduria; inability to convert orotic acid to UMP; megaloblastic anemia (like b12/ thymidine deficiency), but doesn't improve w/ vitamin supplementation; no hyperammonemia like OTC deficiency; tx: uridine supplement
|
|
|
connection between PPP & purine biosynthesis
|
PPP's product ribulose-5-P -> ribose-5-P (substrate of purine biosyn)
|
|
|
explain mycophenolic acid's role (purine synthesis)
|
reversible inhibitor of IMP dehydrogenase. Deprives T & B cells of key components of nucleic acid; immune suppressants; to prevent graft rejection
|
|
|
explain methotrexate's role (purine synthesis)
|
inhibit reduction of DHF -> THF. Slow down DNA replication; chemotherapy
|
|
|
explain allopurinol's purpose and mechanism
|
treatment option for gout; inhibits xanthine oxidase; xanthine more soluble than uric acid
|
|
|
explain adenosine deaminase deficiency
|
excess ATP/ dATP inhibits ribonucleotide reductase -> prevent DNA synthesis; inability to complete DNA synthesis in B & T cells -> Severe Combined Immunodeficiency Disease
|
|
|
explain Lesch-Nyhan syndrome
|
deficiency of HGPRT; can't salvage hypoxanthine/ guanine; elevated PRPP, decreased IMP, GMP -> elevated purine biosynthesis -> gout; tx: allopurinol
|
|
|
How is uric acid secretion modulated in kidney? Examples of the one that promotes reabsorption?
|
uricosuric: inhibit URAT1 -> secretion; antiuricosuric -> keep uric acid; ex: lactate, nicotinate, pyrazinoate
|
|
|
general cause of hyperuricemia & treatment
|
too much synthesis of uric acid or too few excretion of it; allopurinol to reduce synthesis; uricosurics to underexcretors; anti-inflammatory drugs for gout.
|
|
|
what are probenecid or sulfinpyrazone. Which mediator does it work w/?
|
uricosurics; URAT1.
|
|
|
explain cori cycle
|
lactate released by skeletal muscle & RBCs -> turned to glucose by liver -> glucose goes to muscle & RBCs; net loss of 4 ATPs/ cycle
|
|
|
EtOH's impact on biochem
|
Too much NADH -> pyruvate and OAA are both gluconeogenic intermediates, but now they're being diverted to make NAD+ -> decreased gluconeogenesis, TCA cycle inhibited, increase in ketone bodies
|
|
|
sources of two ammonia from urea cycle, starting nw/ glutamine
|
one from oxidative deamination of glutamate by glutamate dehydrogenase & another from transamination of OAA by AST
|
|
|
what is OTC deficiency? Tx?
|
one of urea cycle disorders. One of the enzymes missing. High ortic acid in blood/ urine. Hyperammonemia; restriction of protein intake;
|
|
|
dietary treatment to newborns of urea cycle disorder
|
IV dextrose
|
|
|
phenylbutyrate & benzoate's role
|
in urea cycle disorder: alternative route for nitrogen disposal;
|
|
|
describe hemoglobin; describe type A & F; describe difference.
|
4 polypeptide subunits; each binds heme moiety; cooperative binding; 2 forms: Tense (deoxy)/Relaxed(oxy); HbF: fetal, alpha & gamma, higher O2 affinity; HbA: alpha, beta; HbF has weaker binding of 2,3-BPG (which reduces O2 affinity)
|
|
|
explain bohr effect
|
decrease in pH, increase in temp -> reduces O2 affinity
|
|
|
role of 2,3-BPG
|
reduces O2 affinity; allows body to adjust to environment (anemia, altitude, hypoxia, doping)
|
|
|
saturation curves of myoglobin & hemoglobin -> advantage of sigmoid curve
|
not too adherent, not too loosely adherent for O2 = just right; too adherent -> can't give O2 to tissue; too weak -> gives O2 to any tissue, not the ones that are deoxygenated; this precision is required to accommodate the difference in partial pressure of oxygen from lung & peripheral tissues are different;
|
|
|
mechanism of CO poisoning
|
binds to iron, increases affinity for oxygen; unable to release O2; no O2 -> inhibition of complex 4 for ETC
|
|
|
what forces run the ETC; products of ETC.
|
pH gradient (hydrogen in intermembrane space) & electrical potential (negative in matrix); ATP, CO2, H2O
|
|
|
what are two mobile e- carriers in ETC?
|
CoQ & cytochrome c
|
|
|
steps and constituents of ETC.
|
1 (NADH dehydrogenase), 2(succinate dehydrogenase - FADH2) -> CoQ -> 3 -> cyt c -> 4; ATP synthase/ ATPase (F0, F1)
|
|
|
Describe ATP synthase of ETC
|
F0 (transmembrane); F1: cytosolic; F1 rotates, changing from open, loose, tight (catalytic) conformation; F0 pump H+ down the gradient to fuel ATP synthesis.
|
|
|
what is 2,4-dinitrophenol
|
synthetic uncoupler. Creates proton leak w/o ATP formation; releases heat
|
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mechanism of brown fat; regulation
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beta oxidation -> TCA -> ETC; uncoupling via UCP-1 -> heat.; regulated by norepinephrine & thyroid hormone.
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describe function of rotenone.
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binds complex I of ETC -> no reduction of CoQ from complex 1. reduced efficiency. Complex 2 still functions.
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explain apoenzyme, holoenzyme, cofactor, coenzyme,
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holoenzyme: enzyme w/ non-protein part as activator; apoenzyme: holoenzyme w/o its activator; cofactor: metal ion serving as activator; coenzyme: small organic factor like vitamin as activator
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explain cosubstrate, prosthetic group, synthetase, synthase
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cosubstrate: coenzyme transiently associated; prosthetic group: coenzyme permanently associated; synthetase: requires ATP; synthase: doesn't require ATP
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describe carboxylase
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adds 1 carbon w/ help of biotin
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factors affecting enzyme rxn velocity
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temp: increase T -> increased rxn, until it is too high -> denature; pH: can change ionization of AA residues, extreme change -> denature
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explain steady state assumption
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[ES] doesn't change; same rate of formation as breakdown.
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explain the affect of competitive, un-competitive, noncompetitive inhibitors
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competitive: increases Km; un-competitive: decreased V max and Km; non-competitive: decreased V max
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what is collagen made of, what structure, constituents
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glycoproteins; triple alpha-helix; 1/3: glycine, 1/3: proline, 1/3: hydroxylated proline & lysine
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regulation of collagen synthesis; possible pathology w/o the cofactor
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vitamin c to hydroxylate proline/ lysine -> no H bond; deficient -> scurvy's;
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describe osteogenesis imperfecta: etiology, sx, dx
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point mutation in COL1A1 or COL1A2 genes (type 1 collagen); affect glycine residue; heterozygous -> mixture of abnormal collagen; sx: blue-greyish sclera (blue choroid shown), weakened teeth due to lack of dentin, hearing impairment, brittle bone; dx: skin bx to check fibroblasts, genomic DNA from WBCs to see mutation
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describe pamidronate for collagen synthesis
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tx for osteogenesis imperfecta; anti-resorptive agent for calcium; inhibit osteoclast activity
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describe difference between point mutation & nonsense mutation for osteogenesis imperfecta
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point mutation -> mixture of bad collagen; stop codon: reduced normal, only normal is translated.
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describe folic acid deficiency
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neural tube defects; THF -> methionine -> purine & pyrimidine synthesis; path -> megaloblastic anemia w/o neurological sx;
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Vitamin b12 deficiency (cobalamin)
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THF for homocysteine -> methionine -> megablastic anemia; odd FA accumulation -> neurologic sx
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thiamine (b1) deficiency
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as TPP, coenzyme in formation/ degradation of alpha-ketols, PPP, PDC, BCAA, alpha-ketoglutarate dehydrogenase complex; path: beriberi, Wernicke-Korsakoff Syndrome; reduced ATP production and accumulation of ketoacids
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vitamin c deficiency
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collagen synthesis, iron absorption, norepinephrine synthesis; pathology: scurvy
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vitamin d defiency
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regulate calcium; rickets (bending bone)
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statin drug: mechanism
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targets HMG-CoA reductase as competitive inhibitors
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to differentiate between b12 & folic acid deficiency; pathophysio for that sx
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neuopathy only w/ b12 deficiency; propionyl coA stuck in membrane because b12 also needed for propionnyl coA -> succinoyl coA
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exact reasons for megaloblastic anemia
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increased homocysteine level, reduced emthionine level, impaired formation of THF -> inadequate conversion of deoxyuridylate -> thymidylate -> slow DNA synthesis & nuclear maturation
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distinguish anaplerosis/ cataplerosis
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anaplerosis: refilling intermediate to TCA; cataplerosis: removing intermediate for biosynthetic purpose (gluconeogenesis, FA synthesis, AA synthesis)
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glycolysis: liver vs. muscle
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liver: only during fed, gluconeogenesis in fast; muscle: glycolysis for E. fast and fed; PFK-2 regulation different, spc isoform; liver: PFK2 inhibited by cAMP-dependent phosphorylation when insulin is low; not in muscle; Exercise in muscle: ca2+ -> glycogen phosphorylase kinase, ADP/ ATP -> glycogen phosphorylase, AMP -> allosteric activate PFK1 -> more F1,6BP -> allosteric activate PK, Ca2+ -> activate PDH
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how can much THF mask b12 deficiency? What metabolic reaction is involved?
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while N5-methyl THF -> THF requires B12, when folic acid is high, folic acid -> directly THF by getting dehydrogenated by NADPH; THF is ultimately used to convert homocystine -> methionine
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Purpose of DHFR
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bacteria: make THF; humans: one of two enzymes to make THF
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trimethoprim
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inhibit bacterial DHFR
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methotrexate
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inhibit mammalian DHFR; selective for rapidly dividing cells; chemo
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consequence of medium chain acyl co A dehydrogenase deficiency; tx
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limited beta-oxidation -> not as efficient in deriving energy; prolonged fasting is dangerous; more carb/ protein based diet, avoid fasting; carnithin supplement, because these are used in these patients to excrete medium chain fat via urine
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consequences of atkin's diet
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low insulin, low glycogen -> gluconeogenesis, fat used by muscle, FA used by liver to make ketones
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