Dai1-N-metabolism Flashcards
What are the 3 groups of AA’s based on side chains?
1) charged polar: Lys, Arg, His, & Asp, Glu
2) uncharged polar: Ser, Thr, Asn, Gln, Tyr, Cys
3) non-polar: Gly, Ala, Val, Leu, Ile, Met, Pro, Phe, Trp
What are the essential amino acids?
(Pvt Tim Hall)
- -> Phe, Val, Trp,
- ->Thr, Ile, Met
- ->His, Arg*, Leu, Lys
- we synthesize at a very slow rate
What 2 amino acids do we get from an essential amino acid?
- Tyrosine (from phe)
- Cysteine (from met)
What food has a high BV (biological value)?
- Proteins from animal origin bc they have all essential amino acids
Where are nonessential AA’s synthesized?
- Primarily in the liver
- Almost all (9/11) are made from glucose
What is the amino acid pool?
- 90-100g free AAs in a steady state maintained in our body
- Sources of AAs: dietary protein, body protein breakdown, synthesis of non essential AAs
- Products of AAs: protein synthesis, N-compounds synthesis, glucose, ketone bodies
- AA can be used for E-production during starvation
What is body protein turnover?
-Process in which new protein is synthesized to replace the one degraded. We degrade 1/30th of our proteins daily.
What is Nitrogen balance?
N consumed in diet = N excreted (in healthy state)
What are the 3 scenarios of negative N-balance?
1) Body protein breakdown (metabolic stress)
2) Inadequate dietary protein (Kwashiorkor)
3) Low quality protein ( lack essential AAs)
What are the 2 protein degradation pathways?
1) ATP-dependent ubiquitin-proteosomes
2) Degradative enzymes in lysosomes
What are the phases of protein digestion?
Gastric -> pancreatic -> intestinal
How do zymogens become active enzymes?
- Require a biochemical change
- Ex. hydrolysis, conformational change, etc
How are AAs absorbed?
- Brush border-specific active transport systems in intestines and kidney epithelium
- They all have different but overlapping specificity for AAs
What is Cystinuria?
- Defective AA transporter, important in the kidney
- Low solubility of cystine –> stones
- Excretion of cystine & basic AAs in urine
- Common inherited disease
- Treatment: drinks lots of water to solubilize Cys
What is Hartnup disease?
- Neutral amino aciduris
- Defective neutral AA transporter
- Failure of renal/intestinal cells to absorb neutral aa
- Skin rash, headache, psychiatric symptoms
- Treatment: high protein diet, intravenous/oral nicotinamide (niacin), tryptophan
How is Nitrogen disposed of?
In the liver, a-amino groups are collected in glutamate by:
1) Transamination, released as NH4+
2) Oxidative deamination of gultamate
3) Urea cycle converts it into urea for disposal
How can aminotransferases be used in diagnosis?
- Transaminases are intracellular enzymes, and they leak into blood under pathological conditions
- They are an indication of liver or muscle damage
What is hyperammonemia?
- High levels of ammonia
- Can replace AAs in the diet w/ a-keto acids
- Aminotransferases will then make AAs
- Thr, Lys, Pro cannot participate in transaminations
Why is ammonia very toxic?
- It can cause the reversal of oxidative deamination reaction, which depletes a-ketoglutarate, ATP, and NADH/NADPH.
- Glutamate is an excitatory neurotransmitter, which is made in reverse reaction
What is the urea cycle?
- Series of rxns to convert ammonia into urea
- Complete cycle only in the liver, but partial cycle (local detox of ammonia) exist in other tissues
- Reaction in the mitochondria & in the cytosol
What is BUN?
Blood Urea Nitrogen
- > High BUN: kidney problems
- > Low BUN: genetic defects in urea cycle
How is the urea cycle regulated?
1) amount of enzyme
2) CPS1 activity, rate limiting step. N-acetylglutamate is a required allosteric activator.
What is Hyperammonemia?
- High levels of ammonia
- Autosomal recessive defects
1) N-acetylglutamate synthase(NAGS) deficiency
2) CPS I deficiency
What happens in OTC deficiency?
- Most common; X-linked (increased uracil and oratic acid in blood and urine)
- Episodic hyperirritability, vomiting, lethargy, protein avoidance, ataxia, coma, delayed growth and development, mental deterioration
