SM8 Flashcards
(34 cards)
What are two examples of transamination reactions of alpha keto-acids by aminotransferases?
1) When Alanine aminotransferase (ALT) transfers amino group from alanine to α-ketoglutarate to form glutamate.
2) When Aspartate aminotransferase (AST) transfers amino groups from glutamate to oxaloacetate to form aspartate.
Both requires coenzyme pyridoxal phosphate, a derivative of vitamin B6.
Which AA do not undergo these transamination reactions ?
Lys, Thr, Pro, HO-Pro
Which AA undergoes oxidative deamination to release free ammonia?
Glutamate is the only amino acid that undergoes rapid oxidative deamination, catalyzed by glutamate dehydrogenase.
What cofactors does glutamate DH use?
Either NAD+ (for oxidative deamination of glutamate, the simultaneous loss of ammonia coupled with oxidation of a carbon skeleton) or NADP+ (for reductive amination of alpha ketoglutarate, the simultaneous gain of ammonia coupled with the reduction of the carbon skeleton) as a coenzyme.
The direction of reaction depends on the relative concentrations of glutamate, α-ketoglutarate, ammonia, and the ratio of oxidized to reduced coenzymes.
How does alanine/glucose cycle transfer nitrogen to liver?
During fasting, in the muscle, glucose is oxidized to pyruvate which is TA to alanine though transaminase reaction using ALT. The alanine travels through blood to liver where the ALT transfers the nitrogen from alanine to alphaketoglutarate to form glutamate and then through glutamate DH reaction the nitrogen is released through ammonia ion.
How does purine nucleotide cycle anaplerotically stimulate TCA cycle?
Muscles use lots of ATP, generate AMP and need to recycle it. We use BCAA for nitrogen and one of the byproducts is fumurate a byproduct of TCA which will stimulate the cycle
How is ammonia transported through glutamine?
in peripheral tissues, through reversal of glutamate DH reaction we add ammonia to alphaketoglutarate to form glutamate and then we add another ammonia to form gleaming catalyzed by glutamine synthesis. This goes to liver via blood and the first nitrogen is removed by glutaminase and the second by glutamate DH.
How is urea cycle regulated?
- substrate availability (arginine) in a feed-forward mechanism (see 2)
- allosteric activation of carbamoyl phosphate synthetase I (CPSI) by N-acetylglutamate (NAG, formed from glutamate and acetyl CoA, stimulated by arginine)
- induction/repression of urea cycle enzyme synthesis during high protein diet or during starvation
What are the steps of the urea cycle?
HCO3- in the mitochondrial matrix combines with ammonia through reaction catalyzed by carbonyl phosphate syntheses I (CPSI) (requires 2ATP) to form carbamoyl phosphate. This condenses with orthinine to form citrulline, which is transported to cytoplasm where it condenses with aspartate (a source bringing the nitrogen in). That enzyme is arginosuccinate synthetase (req 2 ATP equiv). That forms arginosuccinate which is cleaved to form fumurate (which can feed into TCA cycle or be converted to malate for gluconeogenesis) and arginine. This is cleaved by arginase to release urea and regenerate orthinine.
What are the nine essential aa?
lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine, and histidine Also tyrosine (made from phenylalanine) and cysteine (made from methionine) are conditionally essential.
What are the branched AA and how are they degraded?
Leucine, Isoleucine and Valine. They are transaminate to an alphaketoacid (req. Vit b6) which is then undergoes oxidative decarboxylation by an alphaketoacide DH. When these DH are defected the branched chain alphaketoacids accumulate in urine to cause maple syrup urine disease characterized by sweet odor. Isoleucine and leucine are further broken down, the first to acetyl CoA (ketogenic) and propionyl CoA which is broken down into succinyl CoA (gluconeogenic) and the second to acetoacetate (ketogenic). Valine also is converted to propionyl CoA to succinyl CoA (gluconeogenic)
What two AA can glycine be made from?
It can be made from threonine and interconverted with serine.
Oxalate is a byproduct of glycine degradation. What happens if it accumulates?
It precipitates as kidney stones.
How is cysteine synthesized?
Met donates Sulfur to homoscyteine which condenses with serine and then through transamination and cleave we form cysteine and alpha ketoglutarate (which can form propionyl CoA feed into TCA cycle)
What happens when enzyme converting Phenylalanine to Tyrosine is defective?
PKU. The enzyme is called phenylalanine hydroxylase.
What are the products of phenylalanine and tyrosine degradation?
fumurate (into TCA cycle) and acetoacetate (ketone body that can be degraded by beta oxidation for energy).
What four disease are associated with the pathway degrading phenylalanine and tyrosine?
PKU, tyrosinemia II, alcaptonuria and tyrosinemia I
What are the bases (purines and pyrimidines)?
Purines = A and G. Pyrimidines = C, T, U. base+sugar = nucleoside. nucleoside + phosphate (1, 2, or 3) = nucleotide.
Where do we get the nitrogen and carbon for synthesis of purines and pyrimidines?
Glycine, Serine, Aspartate and Glutamate
How are purines synthesized?
Ribose 5-phosphate from pentose phosphate pathway and ATP form PRPP and Glutamine to eventually make IMP and then GMP or AMP.
How is purine synthesis different from pyrimidine?
Purine start with ribose ring and build base on it. Pyrimidine start with base and add the ring.
What does ribonucleotide reductase (RR) do?
It removes a oxygen to make deoxyribose ring. Uses diphosphate form of nucleotide as substrate only. Uses thioredoxin which is oxidized and must be regenerated through reduction with thuioredoxin reductase. RR is inhibited by dATP.
How do we get from IMP to AMP and GMP?
We use aspartate and glutamine.
What causes SKID?
Deficiency in the Adenosine deaminase that converts adenosine to inosine.
