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58 Cards in this Set
- Front
- Back
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How do you control regulatory enzyme activity
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- Hormonal control - insulin and glucagon
- Covalent modification - phosphorylation/dephosphorylation - Allosteric modification - availability of substrate - Gene expression - Sensitivity to energy needs of system - ATP/ADP ratio |
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In fed state in liver glucose is converted to _
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Fatty acids - stored in adipose
Glycogen - stored in liver |
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Enzyme responsible for glycogen synthesis and how its regulated
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Glycogen synthase
Insulin dephosphorylates it in fed state - ACTIVATES Glucagon phosphorylates it in fasting state - INACTIVATES |
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Glycolysis does what and major regulatory enzyme
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Conversion of glucose to pyruvate
PFK1 |
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Enzyme responsible for conversion of pyruvate to acetyl CoA and how its regulated
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Pyruvate dehydrogenase - insulin dephosphorylates - ACTIVATES
glucagon phosphorylates - INACTIVATES |
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Which enzyme responsible for conversion of acetyl CoA to palmitoyl CoA and how its regulated
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Acetyl CoA carboxylase - acitvated by insulin by dephosphorylation - RATE LIMITING STEP OF LIPOGENESIS
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How does malonyl CoA prevent futile cycling
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Malonyl coA prevents transport of fatty acyl CoA into mitochondrion - prevents beta oxidation occuring at the same time as FA synthesis thus preventing futile cycling
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Which enzyme breaks down TAG in fed state and how its regulated
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In fed state LIPOPROTEIN LIPASE breaks down TAG into glycerol and FA - STORAGE
Insulin induces synthesis if LPL |
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Which enzyme breaks down TAG in fasting state and how its regulated
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In fasting state TG are broken down by HORMONE SENSITIVE LIPASE which reacts to drop in insulin (not glucagon since glucagon receptors are in liver only)
It breaks it down to glycerol and FA and FA can go to muscle where they burned for energy or they can go to liver where they are burned for energy or used for synthesis of ketone bodies |
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Which hormone stimulates glycogenolysis and how its regulated
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GLUCAGON stimulates glycogenolysis in fasting state - uses covalent modification and gene induction
Glycogen stimulates adenylyl cyclase which starts phosphorylation cascade - glycogen phosphorylase is phoshorylated and it takes off glucose monomers from glycogen and adds P to make G-6-P which is converted to glucose in liver by G-6-Pase (defficiency - Von Gierkes disease) |
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Which hormone stimulates gluconeogenesis and how its regulated
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GLUCAGON stimulates gluconeogenesis by covalent modification and gene induction
Pyruvate dehydrogenase in instead of pyruvate kinase in glycolysis |
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Acetyl CoA Carboxylase requires 3 factors - name them
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ABC
ATP Biotin CO2 |
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What stimulates production of ketone bodies
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Fatty acids inhibit production of malonyl CoA by inhibiting acetyl CoA carboxylase, so instead ketone bodies can be synthesized from acetyl CoA in the liver
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Describe main enzymes for ketone bodies synthesis in liver
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- THIOLASE - in liver only - condenses to acetyl CoA to make acetoacetyl CoA
- HMG CoA synthase - condenses acetyl CoA with acetoacetyl CoA to make HMG CoA - HMG CoA lyase - breaks down HMG CoA to acetoacetate which can be converted to beta - hydroxybuturate and released to the blood where it can be picked up by brain in time of starvation |
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Sequence and source of fuel used by muscle in time of exercise and/or fasting
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1. Glucose from the blood
2. Glucose from muscle glycogenolysis 3. FA from adipose tissue 4. Ketone bodies from liver |
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During fasting what is the source of alanine
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Skeletal muscle releasing AA - go to liver and are source for gluconeogenesis to make glucose
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Describe protein digestion in stomach
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In stomach PEPSIN is a major proteolytic enzyme which cleaves proteins to smalle polypeptides
- Pepsin is produced and secreted by chief cells of the stomach as inactive zymogen PEPSINOGEN - HCl produced by parietal cells of the stomach causes nonconformational change in pepsinogen that enables it to cleave itself to active form - PEPSIN |
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Describe protein digestion in intestine
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- In intestine pancreatic secretions - bicarb and proteolytic enzymes
- Bicarb raises pH - ENTEROPEPTIDASE cleaves trypsinogen and makes trypsin and trypsin can further cleave trypsinogen Trypsin also cleaves CHYMOTRYPSINOGEN to make active CHYMOTRYPSIN Proteases produced by intestinal cells finish breaking proteins to amino acids |
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3 routes of amino acids to blood from intestine
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1. Secondary (driven by hydrolysis of ATP) active Na dependent transport - uptake by cell of Na and AMINO ACID by same carrier protein. Na is pumped from cell into blood by Na/K ATPase while amino acid travels down concentration gradient into blood
2.Facilitated diffusion - from intestinal epithelial cells to portal circulation 3. Gamma glutamyl cycle - |
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Name two genetic defects in membrane transport systems
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Result in decreased absorption of amino acids from intestine and resorption of amino acids by kidney and increased excretion in urine - Hartnup disease and cystinuria
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Cystinuria
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- Defective transport of cysteine - cysteine is synthesized in body and oxidized in cystine which can crystallize forming kidney stones
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Hartnup disease
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Transport of neutral amino acids is defective resulting in defficiency of essential amino acids because they are not absorbed from diet
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Cystic fibrosis
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- Chloride channel protein defficiency
- Poor absorption of proteins and lipids - Glistening, bulky, foul smelling stools - SYMPTOMS DUE TO LACK OF PANCREATIC LIPASES AND PROTEASES |
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Name 2 pure ketogenic amino acids
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Leucine and lysine
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Name all ketogenic acids
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Aromatic acids - phenylalanine, tyrosine, tryptophan
Threonine Isoleucine Leucine Lysine |
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Ketogenic amino acids are converted to
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Acetyl CoA or acetoacetate
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Homocystinuria
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Cystathionine synthase defficiency - homocysteine does not react with serine to form cysteine. Homocysteine that accumulates is oxidized to homocystine and excreted in the urine
Can also have defficiency of methionine synthetase (converts homocysteine to methionine) or dietary defficiency of cofactors - folate and B12 ASSOCIATED WITH HIGH RISK OF CORONARY ARTERY DISEASE ( by peroxidation of LDL particles) |
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Maple syrup urine disease
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Alpha keto acid dehydrogenase is defective - enzyme complex that decarboxylates transamination products of branched chain amino acids
VALINE, ISOLEUCINE, LEUCINE ACCUMULATE Urine has odor of maple syrup MENTAL RETARDATION |
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PKU - phenylketonuria
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Defective conversion of phenylalanine to tyrosine - defect in phenylalanine hydroxylase. Phenylalanine accumulates and is converted to phenylketones - musty odor of urine
MENTAL RETARDATION |
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Alcaptonuria
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Homogentisic acid accumulates (product of phenylalanine and tyrosine metabolism) - HOMOGENTISATE OXIDASE IS DEFECTIVE
Homogentisic acid oxidizes and products polymerize forming dark colored pigments which accumulate in tissues and can be associated with DEGENERATIVE ARHTRITIS |
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Fate of amino acids in fed state
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- Protein synthesis
- Conversion to glucose (if low carb diet) - Excess converted to fat |
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Fate of amino acids in fasting state
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- Converted to glucose or ketone bodies
- Burned for energy |
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B6 - pyridoxal phosphate defficiency
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- Dermatitis, apathy, irritability, susceptibility to infections, convulsions in infants
- Blocks amino acid deamination - Used for transamination and deamination reactions |
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Transamination reactions
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Transfer of AMINO GROUP from one amino acid (which is converted to corresponding alpha keto acid) to alpha keto acid (converted to corresponding amino acid)
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Cofactor for transamination reactions
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PLP - pyridoxal phosphate derived from vitamin B6
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How does muscle get rid off extra N
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Alanine is sent to the liver for gluconeogenesis (glutamine can also be used)
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Which enzymes when elevated indicate leakage from liver because of inflammation
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ALT - alanine transaminase
AST - aspartate transaminase |
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Defects in urea cycle lead to what
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Abnormal mental development and mental retardation
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Hyperammonemia
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High blood concentrations of ammonia lead to tremors, slurred speech or blurred vision. Very high concentrations can lead to coma and death
- Acquired - ammonia detoxificaiton is impaired - circulating levels of ammonia increased - alcoholism, hepatitis or biliary obstruction - Hereditary - defficiency in enzymes of urea cycle - rare, mental retardation within one week of birth |
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Describe mechanism of ammonia toxicity
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Glutamate dehydrogenase catalyzes oxidative deamination of glutamate - ammonium ion is released and alpha ketoglutarate is formed.
IF ammonium is high - reaction will push to the left and there will be lack of NADH and alpha ketoglutarate - which will slow down citric acid cycle and ATP production in ETC |
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Which amino acid speeds up urea cycle
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ARGININE
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Folate is most abundant in
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Green leafy veggies
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Most folate is taken up by _
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liver
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Who needs folate most
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Pregnant and nursing women especially with history of giving birth with neural tube defects
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In folate which nitrogens are most important
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N5 and N10 because they bind directly to the carbon that is being transfered
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Folate has 3 important oxidation states - what are they
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Folate
Dihydrofolate Tetrahydrofolate |
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What can tetrahydrofolate do
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Take one carbone from one molecule and transfer to another molecule
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Factors that cause folate defficiency
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- Malnutrition - not enough of veggies or overcooking of veggies, damage to duodenum (folate is absorbed in duodenum)
- Chronic alcoholism - damage to intestinal cells and brush border enzymes, defect in enterohepatic circulation, liver damage, decreased kidney reabsorption |
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46 y. o female with chronic alcoholism and malnutrition, c/o fatigue and muscle weakness - what findings?
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- Anemia
- Macrocytic RBC's - Polysegmented neutrophils - Reduced folic acid in blood |
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Megaloblastic anemia
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- Due to folate defficiency or borderline B12 defficiency
- Caused by shortage of T for DNA synthesis so slowing down division of rapidly dividing cells (RBC) - Tetrahydrofolate shuttles single C off serine to U to make T (DNA base) |
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Name 2 drugs that interfere with folate, reduce DNA synthesis and so are used as chemo drugs
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- 5- FLUOROURACIL - blocks methylation of U to T
-METHOTREXATE- blocks recycling of folate SIDE EFFECT - anemia |
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Vit B12
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- Essential vitamin
- Made by bacteria only - NOT in plants - meat + dairy - Stores in liver for 3-6 years |
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Function of B12
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Methylation of homocysteine and formation of SAM
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SAM
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S- adenosylmethionine - made from methionine and ATP
- METHYL DONOR |
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Defficiency of SAM causes what
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Megaloblastic madness - extreme irritability caused by B12 defficiency - also numbness, tingling, gate disturbance, blind spots and alteration of sense and smell
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Methyl trap hypothesis
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If there is low B12 - folate gets methylated and is trapped forming folate defficiency
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Lack of intrinsic factor in stomach causes
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Defect of B12 absorption in intestine and PERNICIOUS ANEMIA
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Methylmalonyluria
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- Caused by either B12 defficiency or B12 dependent conversion to succinyl CoA
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