Term
| What are the three phases of protein digestion? |
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Definition
| Gastric Phase, Pancreatic phase, and the intestinal phase. |
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Term
| What are the characteristics of the Gastric phase? |
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Definition
- gastrin stimulates secretion of HCl into gastric lumen
- occurs in stomach; pepsin breaks down proteins. HCl denatures proteins
- HCl kills bacteria
- serous cells secrete pepsinogen which converts in low pH to pepsin. |
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Term
| What are the characteristics of the pancreatic phase of protein digestion? |
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Definition
in the lumen of the small intestine, polypeptides are cleaved into oligopeptides and AAs.
- proteolytic enzymes incled trypsin, chymotrypsin, elastase, and carboxypeptidases.
- secretin stimulates the release of HCO3- into intestine to neutralize pH for pancreatic enzymes to be active
- CCK release |
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Term
| What happens in the Intestinal phase of protein digestion? |
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Definition
enzymes produced in the intestinal epithelial cells (i.e. aminopeptidases, di-/tri-peptidases) cleave oligo- di- and tri-peptides into AAs.
- CCK release |
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Term
| What does CCK (cholecystokinin) do? |
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Definition
- stimulates release of degradative enzymes as zymogens
- stimulates release of enteropeptidease which converts trypsinogen to trypsin (trypsin then catalyzes the activation of many other zymogens)
- starts a degradative enzymatic cascade |
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Term
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Definition
defective Lys/Arg/Cys-Cys/Ornithine transporter; impt in kidney: excretion of cystine and basic amino acids.
- low solubility of cys -> kidney stones
1/7,000
treatment: drink water; other ways to solubilize cys. |
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Term
| Neutral amino aciduria (Hartnup disease) |
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Definition
- defective neutral AA transporters
- failure of renal/intestinal cells to absorb neutral AA
- excretion of neut AA in urine
- pellagra-like rash, headache, psychiatric symptoms, etc. (likely due to reduced Tryptophan for niacin and nicotinamide nucleotide biosynth) |
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Term
| Ammonia toxicity... what are the consequences? |
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Definition
- reversal of glutamate oxidative deamination rxn
- depletes a-ketoglutarate, ATP, NAP(P)H
glutamate = Neurotransmitter
fortunately, there's yet another bloody pathway that converts ammonia to urea! yey! |
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Term
| What is the alloseric activator that works at the level of the rate limiting step of the urea cycle, and what is that rate limiting step? |
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Definition
CPSI (Carbomoyl phosphate synthetase I) requires N-acetylglutamate as an allosteric activator.
acetyl CoA + glu --> N-acetyl-glutamate
enzyme: N-acetylglu synthase (activated by Arg)
- when Arg is high = lots of AAs so upreg urea cycle
- when Acetyl CoA is high, means is enough energy to fuel the cycle, so activator. |
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Term
Hyperammonemia (3 types) and what are the symptoms?
(Urea cycle enzyme deficiencies) |
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Definition
Type IA - N-acetylglutamate synthase def
- autosomal recessive
Type I - CPS I def
Type II - Ornithine transcarbamylase def
- x-linked; affecting males more than female counterparts
Effects:
- Excess N accumulates in gly (when NH3+CO2) and Glu (when NH3+a-KetoGlu)
- 1/30,000 live birth
- coma, brain damage, potentially lethal
Note: inherited or aquired |
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Term
| Citrullinemia (a urea cycle enzyme def) |
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Definition
- arginosuccinate synthase def.
- citrulline can be excreted so not as severe |
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Term
| Arginosuccinic aciduria (a urea cycle enzyme def) |
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Definition
- arginoccunase (arginosuccinate lyase) def.
- arginosuccinate can be excreted |
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Term
| Argininemia (a urea cycle enzyme def) |
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Definition
- arginase def
- arg excreted
- extremely rare; developmental abnormalities |
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Term
| Whate are the general treatment regimens for urea cycle enzyme deficiencies? |
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Definition
- dietary restriction: low protein diet, supplement a-keto acids
- arginine supplementation: provide substrate and a positive stimulator to facilitate the remaining urea cycle machinery |
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Term
| How and where can glutamine be made to release a free ammonium? |
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Definition
| Hydolysis by glutaminase in the liver mitochondria, kidney (to regulate pH), and intestine. Glutamate becomes glutamine. |
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Term
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Definition
| glutamate dehydrogenase catalyzes the oxidation of glutamate into a-ketoglutarate, while reducing a NAD+ and releasing a free ammonia. |
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Term
| Which AAs can release ammonia? |
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Definition
- Glutamine (hydrolysis by glutaminase releases ammoniUM)
- Asp (hydrolysis by asparaginase)
- Ser/Thr (by ser/thr dehydratase rxn)
- Histidine (by histidase)
- Glycine (gly cleavage complex (releases CO2)) |
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Term
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Definition
- intestine (where urea is hydrolyzed to ammonia)
- when urea excretion is compromised, more urea back to intestine |
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Term
| Describe the local ammonia detox mechanism and where it occurs. |
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Definition
| Muscle, liver and brain. Glutamine synthetase catalyzes the conversion of Glutamate to glutamine using an ATP and NH4. |
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Term
| Nonketotic Hyperglycinemia |
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Definition
- defect in glycine cleavage complex
- increased glycine in blood
- severe mental retardation; death in infancy. Glycine is an inhibitory NT, acting on the spinal cord and brain stem. |
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Term
| Which AAs are only ketogenic? |
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Definition
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Term
| Which AAs are both keto- and gluco-genic? |
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Definition
Tryptophan
Tyrosine
Threonine
Isoleucine
Phenylalanine |
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Term
| Maple Syrup Urine Disease |
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Definition
- def in branched-chain a-keto acid DH
- elevated levels of branched-chain AAs and their a-keto acids in blood and urine
- urine has maple syrup odor
- mental and physical retardation; short life span
- 1/200,000
treatment: diet low in branched chain AAs in early life
some respond to thiamine (Vit B1) b/s branched chain a-keto acid DH uses thiamine pyrophosphate. |
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Term
| What are the branched chain AAs? Descrie the catabolic pathway of the branched chain AAs. What cofactors are required? |
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Definition
Valine, Isoleucine, and Leucine. They are deaminated to a-keto-acids by a aminotransferase (req PLP). Then oxidative decarboxylation by a a-keto-acid DH (req thiamine).
Val -> Succinyl CoA
Ile -> Succ CoA or Acetyl CoA
Leu -> Acetyl CoA |
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Term
| Met degredation pathway... |
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Definition
Met to SAM by SAM synthase. Req energy (ATP to PPi). Then methyltranferases to S-adenosylhomocysteine to homocysteine. Serine is added (by cystationine synthase) to make cystathionine. Cystathioase to cysteine and a-ketobutyrate + NH4. a-ketobutyrate is decarboxylated to propionyl coA.
Note: Homocysteine can be converted back to Met (using B-12 cofactor).
-Enzyme - homocysteine methyl transferase. |
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Term
| What two rxns in the body use vit B-12 (cobalamin) as a cofactor? |
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Definition
Homocysteine --> Met
Methylmalonyl CoA --> Succinyl CoA |
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Term
| Methylmalonic Acidemia (MMA) |
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Definition
- recessive genetic disorder
- 1/48,000 newborns
- Sx - labored breathing, uncontrollable vomiting, gastric distress
- high levels of methylmalonic acid, urine contains high levels of ketones. |
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Term
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Definition
- def in UMP synthase
- accum of orotate
- regulation lost b/c increased PRPP and decreased inhibitory end product will both upregulate pyrimidine synth!
- abnormal growth/development (heart and CNS defects), megaloblastic anemia, urinary tract symptoms due to formation of crystals from orotate
treatment: diet rich in uridine (will decrease de novo synthesis... Uridine --> uracil --> UMP) |
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Term
| Various sources of NH3 in the body |
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Definition
- Protein degredation
- Purines and Pyrimidines
- Bacterial Urease
- Amine oxidase
- Hydrolysis of glutamine by glutaminase (liver mito, intestine, kidney) |
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Term
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Definition
- amt on enzymes based on diet (high protein = increased enzymes)
- Arg activat +N-acetylglutamate synthase causes increased N-acetyl-glutamate |
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Term
Folic Acid Deficiency
- normal requirement?
- causes of def
- diagnosis
- consequences |
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Definition
req - 100-200 micrograms/day
causes - inadequate intake, imapaired absorption, impaired metabolism, increased demand
diagnosis - test dose of His and check urine for formiminogluatamate in urine
consequences - defective purine/pyrimidine synth (hematopoetic effects), defective gly cleavage (neuro effects), defective homocysteine conversion (neuro effects) |
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Term
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Definition
- IF deficiency
- impaired b12 absorption
- less THF
- hematopoeteic anc neuro effects (why?)
treatment: folate supplement |
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Term
| Describe Heme Degredation |
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Definition
| After 120 days, RBCs die and go to reticuloendothelial system (liver and spleen). Heme is degraded to biliverdin then bilirubin. Bilirubin complexes with serum albumin and is actively taken up by the hepatic cells. Bilirubin is conjugated by UDP-glucoronyltransferase to become bilirubin diglucaronide. That is released in the bile. It is unconjugated in the intestine by bacterial enzymes. Then billirubin is converted to urobilinogen which is mostly excreted in the feces as urobilin (stercobilin) and some in the urine as urobilin. |
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Term
| What is phsyiological Jaundice? |
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Definition
increased level of unconjugated bilirubin in newborns because of low level of UDP-glucaronyltransferase (liver not fully developed).
-mild jaundice doesn't require treatment but severe requires treatment with fluorescent light |
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Term
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Definition
- def in UMP synthase (can't be absence)
- accumlation/excretion of orotate
- regulation lost because no end product inhibition and increased PRPP will activate)
- abnormal growth and dev (heart/CNS), urinary tract symptoms from orotate crysitals. megaloblastic anemia
treatment: diet rich in uridine
uridine->uracil->UMP (decrease the de novo!) |
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Term
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Definition
| Neurological and gout effects due to lack of HGPRTase. The salvage system doesn't work well. The brain takes a big hit because of low GTP. This causes BH4 def. Defects in NT synth. Increased purine degredation products will result in high uric acid and therefore gout. Allopurinol is the treatment; it reduces the urate concentration but does nothing for neurological symptoms. |
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Term
| Gout primary and secondary causes |
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Definition
Primary: inborn errors of metabolism resulting in high uric acid
- PRPP synthetase mutations
- HGPRTase def
- Glc6Pase mutation
Secondary: renal diseases causing decreased excretion of uric acid
Treatment: allopurinol |
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