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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
Transcription
•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
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+
(Glutamate)
• Deaminates
glutamine to alphaketoglutarate
• Produces ammonia
(Glutamate)
Transamination
• Serum glutamatepyruvate
transaminase
(SGPT)
(glutamate)
– Transfers nitrogen
from Glutamate to
pyruvate which is
transaminated to
alanine
(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 steps
1) Synthesis of carbamoyl
phosphate
– Requires ATP
2) Formation of citrulline
3) Formation of
argininosuccinate
4) Formation of arginine
5) 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, Norepinephrine
• 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
•
•
•
Gut peptides
–
Gastrin
•
•
–
–
Increases GI motility
Synthesized in gut, pancreas and hypothalamus
Bombesin (Gastrin releasing peptide)
•
•
–
Stimulates bile release in response to fat in small intestine
Synthesized in I cells of small intestine
VIP
•
•
–
Stimulates secretion of HCl
Released from G cells in stomach, pancreas and
duodenum
CCK
•
•
Stimulates gastrin release
Released from terminals of Vagus nerve
Secretin
•
•
•
Cell proliferation and inhibition of apoptosis
Produced in Liver
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