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178 Cards in this Set
- Front
- Back
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asparagine
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polar
uncharged amide |
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cysteine
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polar
uncharged sulfur containing forms disulfide bonds with itself |
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lysine
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basic
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arginine
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basic
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histidine
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basic
in RBC gives hemoglobin its buffer effect |
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glycine
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1/3 of a.a. in collagen
greatest flexibility non polar |
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valine
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hydrophobic
nonpolar |
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isoleucine
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hydrophobic
nonpolar aliphatic |
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phenylalanine
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aromatic
hydrophobic rings stack |
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threonine
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polar
uncharged hydroxy H bonds |
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tryptophan
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aromatic
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alanine
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hydrophobic
nonpolar aliphatic |
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serine
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polar
uncharged hydroxy H bonds |
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leucine
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hydrophobic
nonpolar aliphatic |
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proline
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nonpolar
aliphatic RIGID 1/6 of collagen |
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aspartate
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acidic
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glutamine
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polar
uncharged amide H bonds |
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methionine
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polar
uncharged sulfur containing can donate CH3 initial acid in protein |
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thyrosine
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aromatic
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glutamate
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acidic
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reactions to reverse irreversables of glycolysis
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glucose 6-phosphatase
fructose 1,6-diphosphatase pyruvate carboxylase and phosphoenolpyruvate carboxykinase (PEPCK) |
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three carbon sources of gluconeogenesis
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lactate, glycerol, amino acids
fatty acids can't contribute |
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Why do drug level in the blood go up when alcohol is consumed?
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Alcohol competes for cytochrome P-450 which detoxifies many drugs. It oxidizes ethanol.
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Big problem with ethanol metabolism?
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leads to production of lots of NADH. NAD+/NADH ratio is thrown off, malate can't convert into oxaloacetate, lactate can't convert into pyruvate, decreases gluconeogenesis.
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what does pentose shunt do?
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produce NADPH for use in fatty acid synthesis and ribose for nucleotide synthesis
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where is the pentose shunt?
where is it active? how is it regulated? |
cytosol of cells
active in adipose tissue, liver, lactating mammary tissue regulated by NAD/NADH ratio |
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pentose shunt
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important in RBC metabolism, NADPH is antioxidant for RBC
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What is G6PD-deficiency?
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Hereditary disease, eliminates the pentose shunt pathway, leads to break down of RBC in presence of oxidant drugs because they are oxidized
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What is the glucuronic pathway?
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makes glucuronate to synthesize glucuronides to detox waste (xenobiotic substances)
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Characteristics of GAGS
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1. repeating disaccharide unit made of amino sugar and uronic acid
2. N-acetylglucosamine is eterified with sulphate 3. polysaccharide is usually covalently linked to a protein (forms a proteoglycan) |
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Purpose of GAGS
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Form viscouse solutions (e.g. synovial fluid) connective tissue (cartilage/tendons)
Heparin is a GAG (anticoagulant) |
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Glycoprotein function (proteoglycan)
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secretory proteins, membrane components
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What did "Girl Without a Belly Button" prove?
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linolenic acid "omega-3" fatty acid is essential nutrient (last one to be discovered)
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Why is linolenic acid "essential" when only 1 enzyme is missing in its production?
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It may be a food signal to the body
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How many essential amino acids?
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10
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Can't absorb molybdenum?
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Seizures
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Transiron elements necessary for humans?
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Selenium, molybdenum, iodine. Only made in supernovas
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Importance of iodine
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Food signal, why we need tyroid gland
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Which evolved first, food or life?
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Food, first enzymes broke down food
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How do you alkalinize a person
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Sodium and Potassium Citrate (Citrate is turned into CO2 and is exhaled)
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If pCO2 goes up by 10mmHg, what happens to pH?
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goes down 0.1
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Effects of narcotics
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mimic endorphins, reduce respiration, cause respiratory acidosis.
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Major blood plasma ions
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Na+, Ca2+, Cl-, HCO3-, protein
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Major interstitial ions
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Na+, Cl-, HCO3-
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Major cell ions
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K+, Mg2+, HPO42-, protein (big negative)
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Anion gap
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([Na+]+[K+]) - ([Cl-]+[HCO3-]) should be less than 18 mEq/L
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What if anion gap is more than 18?
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There is some other anion in the blood (e.g. lactic acid) indicative of metabolic acidosis
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Main physiological buffer in blood
other buffers: |
proteins (N-terminal amino groups)
bicarbonate buffer, hemoglobin |
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What does carbonic anhydrase do? What happens if inhibited?
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Speeds up conversion of CO2 gas and bicarbonate. If inhibited bicarbonate is not converted and is an osmolite (acts as dihuretic).
If genetically mutated, can have chronic acidosis, leads to thick bones. |
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Glucuronic acid
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Secretion into urine, oxidation at C-6
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Gluconic acid
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oxidation at C-1, turned into glycogen or used in cell
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How do common sugars get transported across brush border cells?
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Galactose = 110 active transport
Glucose = 100 active transport Fructose = 43 Facilitated diffusion Others = 17 Simple diffusion |
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What is glycemic index?
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a measure of the effects of carbohydrates on blood sugar levels (some carbs don't raise blood sugar very much, some do a lot)
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Do you need ATP to get across brush boarder membrane via GLUT2?
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No, just Na+. Need ATP to keep Na+ gradient though
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Where is insulin needed?
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Transport into adipose tissue and muscle only!! (GLUT4 transporter)
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What else does insulin do?
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Signals hepatocyte to make more glucokinase - leads to holding sugar in cell
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Vmax of glucokinase vs hexokinase
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glucokinase is way higher
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Where is glucose converted into fructose for use in cells?
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seminal vesicle tissue, lens of eye, peripheral neurons, placenta
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Why can't you give fructose intravenously?
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bypasses rate mechanism in glycolysis (PFK), causes acidosis and hyperurecemia by pushing glycolysis foreward too much
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calcium counter ion
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magnesium
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buffer consists of:
works best when: |
weak acid and its conjugate base
withing 1pH of its pKa |
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hemogolobin goes from T conformation to R when:
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it releases hydrogen ions upon binding oxygen (T = tense, so it doesn't bind. R = relaxed, when it binds)
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myoglobin
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stores oxygen in muscle cells so that it is available for oxidation of fuels
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myoglobin vs hemoglobin
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at low levels of pO2, myoglobin contains more oxygen than hemoglobin (so hemoglobin is effective transporter as it binds in the lungs and releases in tissue)
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positive cooperativity
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In hemoglobin, binding one oxygen makes it easier to bind the rest (first one is hard to bind)
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2,3-BPG effect on hemoglobin
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increase 2,3-BPG, lower binding of oxygen to hemoglobin
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fetal hemoglobin vs adult hemoglobin
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fetal hemoglobin has lower affinity to 2,3-BPG, so it has higher affinity for oxygen
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Bohr effect
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-increase acidity lowers hemoglobin affinity for oxygen
-pH of blood decreases in tissue, causes release of oxygen -pH of blood increases in lungs, reverses process |
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what effects the rate of regulatory enzymes
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substrate concentration, compounds the alter availability of active site, amound of enzyme
velocity of enzyme is most sensitive to changes in concentration of substrate at concentrations BELOW Km, not as sensitive above Km |
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Km
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concentration of substrate at which V is 1/2 Vmax
(the higher the Km, the higher the substrate concentration required to reach 1/2 Vmax) a mutation that decreases enzyme affinity for the substrate would increase Km |
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Products of glycolysis
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2 ATP, 2 NADH, 2 pyruvates
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Hexokinase/Glucokinase
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phosphorylation of glucose, commits glucose to glycolysis, pentose shunt, or glycogen synthesis
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PFK-1
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phosphofructokinase-1
committed step of glycolysis adds another phosphate to fructose 6-phosphate |
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substrate level phosphorylation
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generation of ATP by mechanism of specific reactions in metabolic pathway
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what does lactate dehydrogenase do?
what happens if it is deficient? |
reduces pyruvate to lactate (anaerobic conditions)
produces NAD+ for continued glycolysis also turns lactate turned back into pyruvate in liver if deficient, patient can't do strenuous exercise |
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what's the point of shuttle pathways?
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transfer reducing equivalents across mitochondrial membrane and ultimately to electron transport chain and oxygen
(mitochondrial membrane is impermeable to NADH) |
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glycerol-3-phosphate shuttle
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-the major shuttle
-no metabolite crosses the membrane -uses FAD and DHAP |
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describe malate-asparate shuttle
where does it occur? |
-metabolites DO cross membrane
-oxaloacetate is reduced to malate, which can cross the membrane -oxaloacetate goes to aspartate to go back across membrane ONLY IN LIVER AND HEART |
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Can we use fructose or galactose for glycolysis?
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yes, they are converted into intermediates of glycolysis
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irreversible reactions of glycolysis
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hexokinase/glucokinase
PFK-1 pyruvate kinase ΔG is negative in physiologycal conditions |
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other functions of glycolysis
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generates precursors, e.g. ribose-5-phosphate for ATP, a.a.'s also
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pyruvate kinase (PK) deficiency problems
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hemolytic anemia
Since RBC have no mitochondria, depend of glycolysis for energy, and without PK, RBC have no ATP, RBC can die. Also leads to accumulation of intermediates |
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what do pyruvate carboxylase and PEPCK use (energy wise)?
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1 ATP and 1 GTP to go from pyruvate to PEP
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which enzymes of gluconeogenesis are cytoplasmic?
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all except pyruvate carboxylase which is a mitochondrial enzyme
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how much does it cost to make glucose?
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six phosphate bonds (ATP and GTP)
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where is glucose 6-phosphatase not expressed?
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in the brain and skeletal muscle.
In these tissues glucose produced by gluconeogenesis will not be transported out fo these cells |
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What is the Cori cycle?
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cycle where pyruvate is turned into lactate in muscles and back into pyruvate in the liver
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result of fructose-1,6-bisphosphatase deficiency
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can't undergo gluconeogenesis, patients have hypoglycemia and metabolic acidosis on fasting
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What does dietary fiber have in it? Where does it come from?
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all polysaccharides and lignin not digested
comes from plant cell walls |
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describe hexokinase/glucokinase regulation
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feedback inhibition (glucose 6-phosphate inhibits the enzyme)
normal levels are too low to significantly inhibit the enzyme in liver, could be complicated due to glucose 6-phosphatase creating a "futile cycle" |
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describe PFK regulation
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PFK is rate limiting enzyme
has activators and inhibitors |
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Effect of fructose 6-phosphate on PFK
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activates
increase concentration increases activity of PFK (substrate activation) |
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Effects of ATP, ADP, and AMP on PFK
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at low [ATP] it activates by binding to active site
at high [ATP] it inhibits by binding to allosteric site AMP and ADP is allosteric activator |
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Effect of citrate on PFK
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inhibits by increase affinity of PFK for ATP
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Fructose 2,6-bisphosphate regulation of PFK-1
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-major regulator in LIVER between glycolysis and gluconeogenesis
-produced by PFK-2 -activates PFK, leads to glycolysis -inhibits gluconeogenesis at fructose 1,6-bisphosphate -regulated by insulin/glucagon (phosphorylation/dephosphorylation rxns. inhibited when phosphorylated) |
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activation of pyruvate kinase (PK)
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fructose 1,6-diphosphate
phosphoenolpyruvate (PEP) both allosteric |
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inhibition of pyruvate kinase (PK)
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ATP
Alanine phosphorylation (liver) |
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what stimulates gluconeogenesis?
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release of substrates:
glycerol (from fat cells when insulin is low) lactate (from muscles and RBCs during exercise) aa's (from muscle when insulin is low) |
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pyruvate dehydrogenase as a regulator
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-inactivated when phosphorylated and does not make acetyl CoA
-inactivated during gluconeogenesis |
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pyruvate carboxylase as a regulator
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Acetyl CoA activates this enzyme
leads to gluconeogenesis if ATP and acetyl CoA are abundant leads to TCA cycle if those are not abundant |
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PEPCK as a regulator
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activated by cAMP, fasting activates adenylate cyclase, leading to cAMP
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fructose 1,6-bisphosphatase regulation
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during the fed state, PFK-2 is phosphorylated, so it makes lots of fructose 2,6-bisphosphate. This activates PFK-1 allosterically and inhibits 1-6 bisphosphatase (along with AMP) allosterically
in fasted state gluconeogenesis predominates due to low fructose 2,6-P |
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where is glucose-6-phosphatase found (be specific)
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only expressed in liver so it can release glucose
is membrane bound on ER and kept separate from glucokinase |
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major site of gluconeogenesis and glucokinase
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liver (glucokinase in liver)
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important difference between glucokinase and hexokinase
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as seen in graph on 13-9, in fasting state liver (glucokinase) will not phosphorylate glucose but other tissues will
glucokinase is NOT inhibited by its product |
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glucokinase regulation of insulin
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acts as a glucose sensor for beta cells. when fasting, low glucose, since glucokinase has low Km it doesn't phosphorylate glucose at these levels and keeps glucose in beta cells low, so they don't secrete insulin. when blood glucose goes up, glucokinase phosphorylates glucose, increases ATP and beta cells can then use ATP for secretion of insulin
at low levels of glucose insulin not secreted at high levels, β-cells get glucose and secrete insulin |
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Glut 2 function, where expressed, if stimulated by insulin
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low affinity glucose transport
liver, kidney, β-cells , intestine not stimulated |
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Glut 4 function, where expressed, if stimulated by insulin
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insulin, contractions (stimulated transport)
adipose, skeletal muscle, heart +++ |
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What is the only non-reducing sugar?
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sucrose
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primary sites of glycogen storage?
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skeletal muscle and liver
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glycogen attaches to what protein?
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glycogenin
acts as a primer |
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action of glycogen synthase
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add activated glucose to nonreducing end of glycogen chains
I - independent of modifier activity D - dependent |
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action of amylo-4,6-transferase
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clips off long branches in glycogen and makes new ones with them
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advantages to branching of glycogen
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1. increases solubility
2. creates more places for synthesis/degradation (increases rate) |
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two enzymes that participate in glycogen breakdown
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glycogen phosphorylase
debranching enzyme |
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Glycogenosis type I
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absense of glucose 6-phosphatase activity
liver cannot release free glucose |
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Glycogenosis type V
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mutation in muscle glycogen phosphorylase
cannot release glucose from glycogen in muscles exercise intolerance |
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triggers for glycogen metabolism in
1. liver 2. muscle |
1. levels of insulin/glucagon and epinephrine
2. AMP (indicates need for energy), calcium, epinephrine Note: glucagon only affects metabolism in the liver |
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what does glycogen phosphorylase do?
how is it regulated? |
degrades glycogen for use (ONLY IN LIVER)
active in phosphorylated form (a) less active otherwise (b) glucagon/epinephrine causes phosphorylation (from b to a) |
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regulation of glycogen synthase
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PKA inactivates it by phosphorylation
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what does cAMP do?
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activates protein kinase A,which phosphorylates glycogen synthase (inactivates), which stimulates glycogenolysis
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what is respiration?
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1. generation of an activated 2-carbon fragment
2. oxidation to yield CO2 3. re-oxidation of reduced electron carriers to produce water and ATP |
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where does respiration occur?
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all stages occur in mitochondria
stage 1 and 2 in the matrix, stage 3 in the intermembrane space |
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how is pyruvate oxidized?
what are the products? |
it travels from cytosol into the matrix of mitochondria and is oxidized by the pyruvate dehydrogenase (PDH) complex
products are CO2, acetyl CoA, and NADH |
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what is the free energy change in decarboxylation of pyruvate?
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very negative, essentially an irreversible reaction
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function of pyruvate dehydrogenase (PDH) kinase
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regulates PDH complex by phosphorylation. When phosphorylated, the complex is inhibited
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what activates/inhibits PDH kinase?
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activated by acetyl CoA and NADH
inhibited by ADP and pyruvate |
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Similarities between NAD+ and FAD
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transfer 2e-, reducing potential
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Differences between NAD+ and FAD
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NAD+ transfers electrons as a hydride ion.
FAD can form a radical and donate and accept electrons at same time |
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oxidation vs. reduction
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oxidation - loose e-
reduction - gain e- |
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anaplerotic reactions of TCA cycle
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reactions that replenish depleted intermediates
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pyruvate dehydrogenase (PDH) deficiency
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causes lactic acidosis
can't convert pyruvate into acetyl CoA |
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pyruvate carboxylase deficiency
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another cause of lactate acidemia
can't provide oxaloacetate from pyruvate for TCA cycle ALSO HAS HYPOGLYCEMIA since they can't do gluconeogenesis |
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where is NADH produced in the TCA cycle?
|
oxidation of isocitrate
α-ketoglutarate decarboxylation malate to oxaloacetate (all by dehydrogenases of the named reactants, ex. malate dehydrogenase) |
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where is CO2 released in TCA cycle?
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oxidation of isocitrate
decarboxylation of α-ketoglutarate |
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where is FAD used instead of NAD+?
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succinate to form fumarate
Fad and Fumarate (both F) (by succinate dehydrogenase) |
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where is GTP made?
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succinyl CoA to succinate
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overall energy yield of TCA cycle
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3 NADH, 1FAD, 1GTP
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regulation of TCA cycle
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NADH/NAD+ ratio and ATP levels
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what does electron transport chain do?
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oxidizes NADH and FAD(2H) with O2 to form water and ATP
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which direction does electron chain transfer
|
in order of increasing reduction potential
(increasing affinity for e-) (e.g. from -1.30 volts to 0.21 volts) |
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which direction is amino acid sequence written?
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from amino (N) terminus on left to carboxyl (C) terminus on right
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energy value of CHO and fat?
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4 kcal per gram of CHO
9 kcal per gram of FAT |
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how much carbs vs fat in the body?
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about 503g (2012 kCal) carbs
12000g (108000 kCal) fat |
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what happens to excess protein? (catabolism)
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excess protein is converted into glucose and fat
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what is hereditary hemochromatosis?
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common genetic disorder, excessive iron absorption, we can't excrete iron
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how is urine buffered?
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using ammonium ions which come from amino acid catabolism. ammonium is toxic to neural tissue
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does the absolute concentration of a H+ anion determine the pH?
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no, it is the RATIO of anion- and H+anion
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what is the role of carbonic anhydrase? what happens if inhibited?
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conversion of dissolved CO2 and carbonic acid
if inhibited slightly - diuretic if inhibited a lot - acidosis |
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what is a transition state analogue?
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acts as an enzyme inhibitor
bind more tightly to the enzymes than the substrates do enzymes commit suicide |
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where does glycolysis take place?
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cytosol
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what are the different types of aldolases? where are they found?
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A - in all tissue
B - in liver C - in brain |
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what does deficiency in aldolase B do?
|
hypoglycemia, vomiting
when people with this deficiency consume fructose, Fru-1-P accumulates which ties up phosphates and also inhibits aldolase A, so gluconeogenesis in the liver is impaired (may be noticed the first time an infant is given fruit juice) |
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how much energy does it take to make glucose?
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6 ATP
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what are gangliosidoses?
|
disease due to genetic deficiency of the degrading enzymes which mediate turnover of gangliosides, compounds accumulate and cause slow progressive deterioration of nervous system function
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soluble vs insoluble fibers
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soluble - degraded by colonic bacteria
insoluble - excreted in feces, supply laxative properties |
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diverticular disease
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weakness in colon wall due to internal pressure, fiber reduces symptoms
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recommended daily fiber
|
children: 19 grams/day
adults: 20-35 |
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what does PKA lead to?
how is PKA regulated? |
release of glucose by inhibiting glycogen synthase
cAMP |
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what does protein phosphatase 1 do? (PP-1)
|
builds up glycogen by deactivating glycogen phosphorylase and stopping PKA from deactivating glycogen synthase
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what does G-subunit do?
|
helps PP-1 bind to glycogen to do its job
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differences between skeletal muscle and liver
|
glucagon has no effect on skeletal muscle
AMP is activator of muscle glycogen phosphorylase, but not in liver muscle contractions release calcium which leads to activation of phosphorylase kinase (break down glycogen) glucose is not activator of muscle glycogen synthase glycogen is stronger feedback inhibitor of muscle glycogen sythase than in liver |
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what does phosphorylase kinase do?
|
activates glycogen phosphorylase
|
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why is coenzyme Q special?
|
not protein associated, it's lipid soluble, only one that can move back and forth across membrane
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importance of NADH dehydrogenase
|
complex 1, starts electron transport chain (NADH)
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which complexes pump protons?
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1,3,4
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ATP per O2
|
NADH - 3atp
succinate - 2atp (because it starts at complex 2) |
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classes of electron carriers
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quinones, cytochromes, iron sulfur centers, copper ion
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complex 2
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succinate
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complex 3
|
cytrochrome b-c
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complex 4
|
cytochrome c oxidase (to water)
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what is somogyi reaction
|
body overreacts to low blood sugar
|
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effects of dinitrophenol (DNP)
|
picks up protons in intermembrane space, diffuses accross membrane and releases in matrix, throws off gradient (uncoupler)
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where are natural uncouplers? what for?
|
brown adipose tissue, produce heat
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what is limiting factor in Ox/Phos in most tissue? what might chance that?
|
ADP, but O2 is during exercise or ischemia, and reduced substrates are limiting with dietary deficiencies
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Dihydroxyacetone phosphate shuttle
|
used to get reducing equivalents across mitochondiral membrane using DHAP and G3P (G3P is protonated and can travel across membrane)
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how are reactive oxygen species (ROS) produced?
|
oxidative phosphorylation by accident
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thiamine deficiency leads to...
|
accumulation of pyruvic acid and alpha ketoclutaric acid
|
