Biochem 2-4 Urea Cycle & Nitrogen Metab

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positive nitrogen balance

Back 1

input>output

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negative nitrogen balance

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output>input

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essential amino acids

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PVT TIM HALL- phe, val, trp, thr, iso, met, his, arg, lys, leu

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tyrosine is made from

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phenylalanine

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cysteine synthesis requires

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methionine's sulphur

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although essential for growth, _______ is also generated in the urea cycle.

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arginine

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Urea cycle activity is highest when

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you've just eaten protein or you've been fasting and AA's are being used for GNG

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Breakdown of AA's generates ammonia because

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The N component can't be used and must be excreted as urea, ammonium, creatinine, and uric acid

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Hypercatabolic State

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increased fuel usage due to injury, trauma, infection; negative N balance

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Alanine, Aspartate and Glutamate can be transaminated from

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Pyruvate, Oxaloacetate, and alpha-Ketogluterate respectively

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protein digestion starts in the

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stomach

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AAs can't be further catabolized until

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the amino group is removed through transanimation or deanimation

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Transanimation Rxn:

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amino acid + α-KG → α-keto acid + glutamate; the nitrogen is now on glutamate.

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Aspartate's α-keto acid is:

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Oxaloacetate; likewise, alanine's α-keto acid is pyruvate, and glutmate's α-keto acid is α-ketogluterate

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transanimation is catalyzed by

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aminotransferases... what do they do? Transfer amino groups to another AA!

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AST

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aspartate aminotransferase... aspartate↔OAA

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ALT

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alanine aminotransferase... alanine↔pyruvate

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T/F: transanimase reactions are reversible

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true; direction is concentration dependent

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Pyridoxal Phosphate (PLP)

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aminotransferase cofactor; used to transfer amino group in aminotransferase Rxns; synthesized in the liver from B6 (pyridoxal); aminotransferase and transanimase are used interchangeably

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Glucogenic AAs

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Ultimately degraded to Pyruvate or TCA intermediates (a-ketogluterate or after)

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Ketogenic AAs

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Ultimately degraded to acetyl CoA or acetoacetate

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Insulin effect on AA metabolism

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Promotes AA uptake and protein synthesis

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Glucagon effect on AA metab

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Stimulates AA uptake in the liver

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Glucocorticoid (Cortisol) effect on AA metab

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Induces Ubiquitin synthesis; Stimulates GNG, so liver uptake of AAs for precursors stimulated

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Skeletal m. has lots of _____ AAs

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branched chain

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Branched Chain AAs

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val, leu, ile

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Fasted Skeletal m. AA metab

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branched chain AAs released from protein are oxidized in muscle for energy or export (as a-keto acid) to other tissues for energy use

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glutaminase

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glutamine→glutamate + NH4; occurs in the liver

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Glutamate Dehydrogenase

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Deaminates Glutamate to α-KG; ammonia and NAD(P)H released in forward direction; nitrogen goes to urea cycle

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T/F: Glutamate DH is a reversible enzyme

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true: occurs primarily in liver and kidney; can also occur in skeletal muscle if you need to regenerate a-ketogluterate.

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glutamate DH

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glutamate+NH4→α-KG+NH4

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Transanimation Rxns: The amino acid gives its amine group to _____, thus producing _____. The original amino acid has been converted to its corresponding _____.

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α-KG, glutamate, α-keto acid

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In muscle and other tissues: glutamate+ NH4→_____. What enzyme catalyzed this rxn?

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glutamine; catalyzed by glutamine synthase; glutamine can then carry 2 ammonia molecules to the liver

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Deamination of glutamate by ____ in the liver releases nitrogen which can go into the urea cycle

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glutamate dehydrogenase; glutamate→α-KG+NH4

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Deanimation by Glutamate DH in muscle regenerates:

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a-KG, which is great 'cuz you can break down more branched chain AAs, but bad 'cuz you end up with free ammonia in muscle cells.

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Name 3 processes producing free ammonia

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purine metab, bacterial metab in gut, serine and threonine metab

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Only the _____ can get rid of free ammonia.

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liver

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Glutamine can carry ___ ammonia molecules to the liver.

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2

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Name 3 AAs that can transport ammonia to the Liver:

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Glutamate, Glutamine, Alanine

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Lots of _____ is available in muscles and can be transaminated to alanine.
In the liver, alanine gives the amino group back to _____
This process regenerates pyruvate in the liver.

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pyruvate, glutamate, pyruvate

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Urea cycle occurs in the______

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liver; disposable form of ammonia transported in blood for excretion

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CPS1

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HCO3- + NH4+ → Carbamoyl Phosphate; 1st step of urea cycle; mitochondrial

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OTC

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Carbamoyl Phosphate + Ornithine → Citruline; 2nd step of urea cycle; mitochondrial

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CPS1 & OTC occur w/in _____.

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mitochondria

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What intermediate immediately preceeds Urea?

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Arginine

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What is the product of OTC and what happens to it?

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citrulline; crosses mitochondrial into the cytosol for urea cycle processing.

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All steps following CPS1 and OTC occur in the:

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cytosol

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Where does the OTC substrate ornithine come from?

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leftover as urea is cleaved from arginine; ornithine crosses into the mitochondria to be made into citrulline, which leaves the mitochondria to continue the urea cycle.

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Does the urea cycle require energy? Is it reversible?

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yes, no

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Urea Cycle rate limiting step?

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CPS1

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The first N in the urea cycle comes from______, the second comes from ________.

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ammonia, aspartate

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Can urea cross membranes?

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yes; it has to in order to diffuse into the blood for transport to kidneys.

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bacterial urease

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intestinal bacteria that cleave urea→ammonium

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BUN

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blood urea nitrogen; measure of [urea] in blood; reflects kidney and liver function as well as diet and nutritional status

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Kidney failure increases or decreases BUN?

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increase due to reduced excretion

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High protein diet increases or decreases BUN?

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increase due to more urea being produced

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Liver failure increases or decreases BUN?

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decreases due to less urea being produced

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Does overhydration increase or decrease BUN?

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decrease due to dilution of blood

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Malnutrition/starvation increases or decreases BUN?

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decrease; more urea due to muscle breakdown, but low BUN due to low dietary protein.

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NAG

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n-acetylglutamate: allosterically activates CPS1; synthesized from acetyl CoA + Glutamate