Amino Acid Degredation and The Urea Cycle Flashcards
1
Q
Proteolysis
A
-the breakdown of protein to free amino acids
2
Q
The amino acid pool
A
- is an abstraction used to represent several compartments in the body which vary in their pattern of amino acids as well as their concentrations
- in intracellular compartments the concentration is considerably higher than in the extracellular compartment, this gradient is maintained by active transport of amino acids into cells. The size of the gradient varies with the different amino acids, being greatest with glutamate and glutamine
- glutamine and alanine are the most abundant amino acids in serum
- amount of free amino acids- in the body there is about 100g of free amino acids, of which 100g amino acids, 50% glutamate and glutamine, 10% essential amino acids
3
Q
Essential amino acids
A
- these are carbon skeletons that cannot be synthesized by humans and are essential dietary factors
- 10 are essential
- histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, arginine (for growth)
4
Q
Non-essential
A
- alanine, arginine, asparagrine, aspartate, cysteine (Made from methionine), glutamate, glutamine, glycine, proline, serine, tyrosine (made from phenylalanine)
- cysteine becomes essential if methionine is low and tyrosine becomes essential if phenylalanine is low
5
Q
Inputs to the amino acid pool
A
gastrointestinal inputs:
-70-100g of dietary protein and 35-200g of endogenous protein from sloshed off intestinal cells absorbed daily
6
Q
Cystic fibrosis
A
- patients defective in pancreatic secretions, must supplement with pancreatic enzymes
- defect in the chloride channels in the pancreastic secretory ducts , they harden and eventually block, leading to a lack of pancreastic enzymes in the intestinal lumen to digest proteins
7
Q
Absorption in the small intestine
A
- five separate systems have been identified for the transport of amino acids from the gut into intestinal epithelial cells. These five overlap considerably in their specificity
- disorders associated with defects in amino acid transporters lead to increased levels of these amino acids in the urine, since the same transporters are used in renal tubules
- most cases disorders are benign, or cause minor problems since amino acids are also absorbed from the intestines as small peptides by a separate transport system
8
Q
Important points of absorption
A
- 5 separate transporters
- all Na or proton symporters
- same transporters in kidneys
- high degree of redundancy
9
Q
Hartnup’s Disease
A
- a defect in the transport system for neutral and aromatic amino acids from the gut and the renal tubules
- Symptoms: similar to pellagra (niacin deficiency, 4D’s: Diarrhea, Dermatitis, Dementia, Death_
- Treatment: administration of niacrin
- Diagnosis: symptoms of pellagra with high levels of neutral and aromatic amino acids in the urine and feces
10
Q
Cystinuria
A
- a defect in the transport system for basic amino acids and cystine (a disulfide-linked dimer of cysteine) from the gut and the renal tubules
- Symptoms: cystine is relatively insoluble and forms crystals which can lead to urinary tract infections and kidney stones
- Treatment: fluids, and adminstration of the drug penicillamine, which reacts with cystine for form a significantly more soluble compound
11
Q
Transcytosis
A
- across the brush border membrane
- most pronounced in infants where it enables them to acquire antibodies from breast milk
- this can also cause problems in infants where it can lead to allergies to various proteins in their food
12
Q
Proteolysis of endogenous proteins
A
- body protein is continuously being broke down to free amino acids
- the rate of this varies widely between proteins from half lives of a few minutes to years
- for a 70 kg man, about 400 grams of protein turn over per day
- 50 grams undergoes oxidative degradation and is replaced
- Measure of protein breakdown- histidine residues of muscle protein actomyosin are methylated posttranslationally. When actomyosin is broken down, 3-methyl histidine is liberated and excreted into the urine. The urinary levels of this compound can provide a measure of muscle protein breakdown
13
Q
Outputs from the amino acid pool
A
- protein systhesis- translation OR
- catabolism of amino acids- Metabolic breakdown of amino acids to urea and Co2 is a continuous drain. This is reduced during starvation, but is never turned off. Hence there must be a daily intake of amino acids to replenish the pools (USRDA 40-50g/day) from 12 to 20 grams of nitrogen (from amino acids) is excreted per day, principally as urea
14
Q
Nitrogen Balance
A
- if total daily loss in urine, skin and feces is equal to daily intake- in balance
- positive balance- losses are less than intake, children and convalescing adults
- negative balance- losses are more than intake, as in starvation or wasting diseases, prolonged could be fatal if reaches 1/3 total body protein
- even not enough of one essential amino acid can turn someone to a negative balacne
- animal proteins- high biological value
- plants deficient in lysine, methionine and tryptophan, less concentrated and less digestible than in aminals
- absence of lysine in grains in underdeveloped countries- kwashiorkor
- grains and beans provide complementing- have to eat both
- you will not gain net nitrogen- you will pee off most of it and store away the carbon
15
Q
Amino Acid Degredation
A
-free ammonia ion is highly poisonous so the body can remove free NH4+ in three ways:
-Glutamate Dehydrogenase: take NH4+ NAD(P)H and protons with alpha ketoglutarate and changes it to glutamate and NAD(P)+ and H20
-Glutamine Synthase, reversibly by Glutaminase: glutamate to glutamine using ATP and NH4+ - glutamine is a major carrier of NH4 groups in the blood
-Carbamoyl Phosphate Synthase I and II- NH4+ CO2 +2 ATMP to get the Co2 to carry,
I- in mitochondria for urea cycle, II- in cytoplasm for pyrimidine nucleotide biosynthesis (doesn’t use NH4)
