Protein metabolism

Roles of proteins

• DNA– Only codes for

proteins• Proteins

– Structure and shape– Metabolic capability

Amino Acids

• Building blocks of proteins

• 20 in the human body

• Contain C,H,O and Nitrogen

• Contain– Amine group

• NH2

– Carboxyl group• COOH

• Also contain a side chain– Makes amino

acids different

Amino acids• These make up the

20 AAs in the body– Essential

• Necessary in the diet

– Non-essential• Can be

manufactured– Meat vs vegetarian

diet

Protein structure and function• Proteins

– Made up of AAs– Synthesized in the ribosome– Control: DNA & RNA

• Chromosomes– Genetic information– Contains codes for protein

synthesis

• DNA– Pentose sugar (deoxyribose)– Phosphate group– Organic base (purines; A and G

and pyrimidines; T and C)• A,T,G,C

• Thymine binds Adenine and Cytosine binds guanine

– Parallel strands that run in opposite directions

•DNA strand unravels•Complementary strand of messenger RNA is formed (mRNA)

•RNA polymerase•Uracil (U) replaces T

•This strand contains a copy of the genetic information coded for on DNA•mRNA is translocated from the nucleus to the cytoplasm

Transcription

Translation• mRNA travels to

ribsome– Information on mRNA

codes for particular proteins

– Each amino acid• 3 base pair codon• This is picked up by

transfer RNA (tRNA)• tRNA then brings the AA to

the developing protein chain

Transcriptional and translational control

• Transcriptional– Alteration in the

concentration of mRNA

• Regulation of mRNA polymerase

• Translational– Ribosome– Affects the rate at

which the protein is synthesized

Amino acid metabolism• No excess protein storage

in body– Excess is converted to fat

or sugar or oxidized– Protein turnover is very high

• Repair and maintenance• Enzymes

– Rapid turnover allows them to adapt quickly to changing demands

– E.g. rise and fall in oxidative enzyme activities with training and detraining

• Turnover– Balance between synthesis and

degradation

Amino Acid metabolism

• Transamination– When the amine

group of an amino acid is transferred to another molecule

• This molecule is typically a keto acid– Essentially an AA

without a nitrogen group

Deamination

• Glutamate dehydrogenase– Along with the

coenzyme NAD+• Deaminates

glutamine to alpha-ketoglutarate

• Produces ammonia

(Glutamate)

(Glutamate)

Transamination• Serum glutamate-

pyruvate transaminase (SGPT)– Transfers nitrogen

from Glutamate to pyruvate which is transaminated to alanine

(glutamate)

(glutamate)

Protein metabolism in exercise• Oxidation

– Muscle can only oxidize the following AAs

• Alanine, aspartate, glutamate, leucine, isoleucine, valine

– BCAA» L, I and V» Most important

– However, oxidation accounts for only ~ 5-10% of energetic needs

Problem with protein metabolism

• Nitrogen (specifically, ammonia)– Toxic

• Urea cycle– Converts NH3 to urea,

which is excreted in the urine

– 5 steps1) Synthesis of carbamoyl

phosphate– Requires ATP

2) Formation of citrulline3) Formation of

argininosuccinate4) Formation of arginine5) Formation of urea

Gluconeogenesis• Some AAs are glucogenic

(red), some ketogenic (yellow)

• Some also function to help maintain the Kreb’s cycle (anaplerotic additions)

Biologically important amino acids• Neurotransmitter AAs

– Glycine, glutamate, taurine, aspartate

• Neurotransmitter proteins– Acetylcholine

• Important to muscle contraction

• Synthesis:– Acetyl-CoA and Choline

» Choline acetyl transferase

• Degradation– Acetylcholinesterase

Amino acids• Catecholamines

– Epinephrine, Nor-epinephrine

• Synthesis– Tyrosine

• All the products of this pathway have biological effects

• L-DOPA– Used to treat Parkinson’s

disease– Precursor to dopamine, nor-

epi and epi– Precursor to melanin

• Dopamine– Neurotransmitter– Sympathetic nervous system

stimulant

Amino acids• 5-Hydroxytryptamine

(serotonin)– Neurotransmitter– Synthesized from

tryptophan– Contributes to well-being– Leads to melatonin

• Produced in pineal gland• Important to circadian

rhythms• Powerful antioxidant

Regulatory peptides and proteins• Metabolic regulators

– Insulin• Produced in beta cells

(islets of Langerhans) of pancreas

• Primarily Anabolic – Glycogen storage– Reduced lipid mobilization– Stimulates protein

synthesis

– Glucagon• Produced in alpha cells• Primarily “Anti-insulin”

– Controlled• Basically by the blood

glucose concentration• Somatostatin

– Formed in delta cells– Prevents excessive insulin

release following a meal

Growth factors, gut and brain peptides• Somatomedins

– IGF-1 and 2• Cell proliferation and inhibition of apoptosis• Produced in Liver

• Gut peptides– Gastrin

• Stimulates secretion of HCl• Released from G cells in stomach, pancreas and duodenum

– CCK• Stimulates bile release in response to fat in small intestine• Synthesized in I cells of small intestine

– VIP• Increases GI motility• Synthesized in gut, pancreas and hypothalamus

– Bombesin (Gastrin releasing peptide)• Stimulates gastrin release• Released from terminals of Vagus nerve

– Secretin• Increase water and bicarbonate secretion into the small intestine• Produced by S cells of duodenum

• Brain peptides– Endorphins

• Endogenous morphine• Produced in brain, released via hypothalamus and pituitary