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Production of protein - Coggle Diagram
Production of protein
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Lysosomal
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Proteolytic enzymes within lysosome separated from cytosolic components
MACROAUTOPHAGY - non-selective: ER derived autophagisomes engulf cytosolic proteins/aggregates organelles. Lysosome fuses with this to initiate proteolysis.
MICROAUTOPHAGY-non-selective: Invaginations of lysosomal membrane engulf proteins/organelles.
CHAPERONE-MEDIATED AUTOPHAGY-selective: Chaperone protein hsc70, in cytosol and intralysosomal, accompany specific cytosolic proteins in response to stressors (fasting/ oxidative stress etc).
ENDOCYTOSIS/PHAGOCYTOSIS: Extracellular substances.
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Key players - AA catabolism
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Alanine - glucose-alanine cycle transports nitrogen from AA breakdown from tissues to liver, also recycling C backbone that can be converted to glucose for energy
Glutamine - formed from BCAA degradation in tissues, important metabolic fuel for kidney and gut in fasting state, provides ammonia to buffer proton diuresis in metabolic acidosis states
Cortisol - proteolysis, protein synthesis, gluconeogenesis
Glucagon - glycogenolysis, gluconeogenesis, AA degradation, ureagenesis, entry of AA to liver
Branched chain AA - isoleucine/ valine/ leucine - major AA that can be oxidised in tissues other than the liver, especially skeletal muscle
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Protein Turnover
: faulty/ aging/ obsolete proteins, signal transduction, flexible system to meet protein/ energy requirements of environment
Main means of protein degradation - proteasome (ubiquitin-dependent), lysosome
Ubiquitin: Mark of Death
small protein
carboxyl group forms isopeptide bond with multiple lysine residues
E1 - ubiquitin-activating Ez
E2 - ubiquitin-conjugating Ez
E3 - ubiquitin-protein ligase
Formation of ubiquitin chains
N-terminal rule - N-terminal residues determine protein half-life, PEST sequences (proline, glutamate, serine, threonine), cyclin destruction box
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Amino Acids
: glucogenic - carbon backbone produces glucogeogenic/ TCA cycle intermediates
ketogenic - carbon backbone produces acetyl-coA/ acetoacetyl coA
only leucine and lysine solely ketogenic
Important Hepatic proteins
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albumin
coagulation factors
IGF-1
C-reactive protein
carrier proteins
apolipoproteins (for lipoproteins)
Degradative pathway
: varies - phenylalanine, tyrosine, P-hydroxyphenylpyruvate, homogentisate, 4-maleyacetoacetate, 4-fumarylacetoacetate, acetoacetate + fumarate
OR
Alanine, pyruvate
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Transamination
: amino group (–NH₂) is transferred from an amino acid to an α-keto acid, forming a new amino acid and a new keto acid
Transamination of Alanine
: alanine + a-ketoglutatate --> pyrucate + glutamate (catalysed by alanine aminotransferase)
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Nitrogen Balance
: dietary protein (0.75g/kg/day), metabolic precursors (glycolysis, TCA intermediates, Acetyl-CoA), free AA pool, proteins
renal excretion - 70g/day
faecal loss - 10g/day
skin/hair/sweat loss
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GI Proteolysis and Absorption
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Stomach - dietary protein - HCL, pepsin
Small intestine - denatured protein - chymotrypsin, trypsin, aminopeptidase
Enterocytes - oligopeptides and AAs - enterocyte peptidases, AA in bloodstream, A.T