Protein/ AA Metabolism

Protein basics

¾ of body solids are ptoeins

Composed of amino acids linked via peptide linkages

Protein structure

Amino grou (NH2)

Carboxylic group (-COOH)

Variable side chain (R)

attached to a central alpha-carbon

Hydrophobic side chains

Aliphatic and aromatic sode chains

Aliphatic amino acids

Methionine, cysteine, alanine, proline - nonbranched

Leucine, isoleucine, and valine - branched

Aromatic amino acids

Phenylalaline, tyrosine, tryptophan

Hydrophilic amino acids

Asparagine, glutamine, serine, threonine

Neither hydrophobic or hydrophilic

Glycine - simpletest form of AA

Basic amino acids

Histidine, lysine, arginine

Acidic amino acids

glutamine, aspartate

Essential amino acids

Required in the diet; non sysnthesized by the body

ex: Phe, Val, Thr, Try, Ile, His, Arg, Leu, Lys

Taurine - cats

Glycine - chickens

3 primary sources of protein in the body

Tiissue proteis

Exogenous dietary proteins

Endogenous proteins - sloughed cells, exocrine secretions

Protein storage & transport

35-65mg of AA are store

Polypeptides are rarely absorbed

AA absorbed within 5-10 minutes

must be transported via active transport or facilitated diffusion

Protein storage cap

Excess protein is degraded into other products, utilized for energy or converted to fat/glycogen and stored

Protein decomposition

occurs rapidly under influence of intracellular lysosomal digestive enzymes; cannot be transported back into the blood.

Functional roles of proteins

Osmotic pressure, immunity, blood coagulation

Liable storage medium as liver plasma proteins

Intestinal cells utilize

Gln & Asn for energy production

Skeletal muscles utilize

BCAA’s to transfer amino group to pyruvate/glutamate to form Ala/Gln

Ala is favored by

the liver during gluconeogenesis

Gln is favored by

the Kidneys during gluconeogenesis; source of most renal excretion of NH4+

When is Val release from skeletal muscles?

During starvation; to supply substrates for brain tissue

Oxidized Val does what?

Transfers NH2 group to Glu to form Gln; perferred manner of getting ride of NH3 by the brain

Liver proteins

The catabolism of most AAs start in the liver, except Gln, Asn, & BCAAs

NH2 group transferred to urea or alpha-KG to for Glu/Gln

Carbon skeleton will either be oxidized, used in gluconeogenesis, or used in ketogenesis

Strictly glucogenic AA

Ala, Arg, As, Asp, Cys, Gln, glu, Cly, His, Met, Pro, Ser, Thr, Val

Strictly ketogenic AA

leu

Lys

Glucogenic & Ketogenic AA

Ile, Phe, Trp, Tyr

Alanine is turned into Pyruvic acid via

Transamination; common in the liver

Results of Transamination

AA derivative & AA

Enzyme that drives transamination

Transaminase

Enzyme responsible for deamination

Mitochondria glutamate dehydrogenase (GLDH) - release NH4 from Glu

How is NH4+ detoxified

Incorporation into urea; C-skeleton is sent to TCA cycle > gluconeogenesis or lipogenesis

Urea

primary end-product of N metabolism in mammals; ureotelic

Amminia

primary end-product of N metabolism in fish; ammonotelic

Uric acid

primary end product of N metabolism in birds & reptiles; uriotelic

Where does urea synthesis primarily occur?

In the liver; N transferred from AA to urea via transamination & deamination RXNs

5 RXN of urea cycle

1. carbamoyl phoosphate synthase -1

2. OT

3. ASS

4. AS

   1. Arginase

Krebs-Hanseleit Oenithine Cycle (Urea)

Problems in urea syn. > hyperammonemia

Mitochondrial carbamoyl phosphae formation is rate limitin gsteo

Urea freely diffuses out of hepatocytes

Urea disposal

BUN freely filtered by kidneys & ~50% secreted into urine

25% moves direcly to digestive tract > combine with urease > form NH3 > bac. protein or portal circulation

Positive ntrogen balance

when protein syn. exceeds excretion - associated w growth, lactation, metabolic stress recovery

Negative Nitrogen balance

When there is a net loss of body protein - associated w/ forced immobilization, starvation, esnescene, diabetes m. infection , etc.

Hyperammonemia

Elevated concentration of ammonia

Ammonia intoxication

causes hepatic encephalopathy

depletes alpha-KG, decreasing cellular oxidation and ATP production