Amino Acids Flashcards
Role of proteins/AAs
Breakdown for fuel
Nitrogen excretion in urea cycle
Carbon skeleton cycling
Pathways of protein degradation
Lysosomal
Ubiquitin-protease
Intestinal
Intestinal degradation
Dietary proteins = AAs for oxidative metabolism, gluconeogenesis
Proteins hydrolysed to AA via proteolytic enzymes, enter intestinal cells, and exit to bloodstream
AA handling
No storage form - must be used
AA amino group nitrogen removed – urea, excreted
Carbon skeleton – AcCoA, acetoacetylCoA, pyruvate, CAC intermediates
Can also form glucose, FAs, ketone bodies
Protein turnover
70-100g intake
10-20% of total oxidative metabolism
High rates in structally rearranging tissues e.g. uterine tissue in pregnancy, skeletal in starvation
Low rates in long lasting structural proteins
Oxidative degradation of AAs
Occurs in protein-rich states, starvation (cellular AAs) and in normal processes Carbon skeleton (left from amine removal) is oxidised in CAC
Transamination (Step 1. ox degradation)
Alpha amino group transferred to a-ketoglutarate = glutamate and carbon skeleton
with transaminases
Deamination (step 2.)
Amino group removed from glutamate by glutamate dehydrogenase (GDH) in liver
Regenerates a-ketoglutarate, releases ammonia
Urea cycle
Liver, to detoxify ammonia
GDH (in matrix) mediates deamination = ammonia, sequestered in matrix to prevent cell damage
Urea cycle uses 3ATP equivalents to produce urea (4 part II in notes)
Urea cycle and CAC
Linked via aspartate-argininosuccinate shuttle
Fumarate is also an intermediate in both, converted to malate for citrilline shuttle in CAC
Aspartate, produced by CAC, used for shuttle for urea cycle too
AA carbon skeleton fates
Keto acid produced by transamination (i.e. amino acid with amino group removed), converted to metabolic intermediates by oxidative metabolism Pyruvate Oxaloacetate Fumarate Succinyl CoA A-ketoglutarate Citrate Acetyl CoA Acetoacetyl CoA
Amino acid entry to CAC
Oxidation of AAs allows them to enter the cycle, used for glucose (glucogenic: producing pyruvate/CAC precursor when catabolised) or FAs/ketones (ketogenic: if acetoacetate/precursors are formed)
Gluconeogenesis from AAs
AA and lactate = major precursors, converted to pyruvate
FA synthesis from AAs
Only leucine and lysine are solely ketogenic
Excess dietary AAs converted to fat
Branched chain AA degradation?
Valine, isoleucine and leucine
NOT degraded in liver - only in muscle, kidneys and brain
This is due to an aminotransferase (not present in the liver) = transamination
Branched chain a-keto acid dehydrogenase (BCD) complex then catalyses oxidative decarboxylatoin of a-keto acids, giving CO2 and acCoA
Regulation of branched chain AA degradation?
BCD complex inactivated by phosphorylation when dietary AA are low
AA diseases
Maple syrup urine disease - missing/defective BCD complex = accumulation of a-keto acids and AAs
Phenylketonuria
Absence of phenylalanine hydroxylase or cofactor = no phenylalanine degradation
Nitrogen transport
To liver for urea synthesis
Branched chain AAs contribute a lot of nitrogen = toxic ammonia
Transported as glutamine (glutamine synthetase combines glutamate + ammonia = glutamine)
Or as alanine
(alanine transaminase converts pyruvate to alanine in alanine cycle)
Alanine cycle
Two transamination reactions, in muscle and liver
a-amino group from glutamate – pyruvate, leaving alanine
Alanine – liver, reverse occurs by transamination = a-ketoglutarate and pyruvate
Catalysed by alanine transaminase
Overall route of AAs?
AAs – liver for disposal and carbon harvest – liver for glucose synthesis
Regulation of AA degradation
Substrate concentration (enzymes have high Km = MM kinetics) Glutamate dehydrogenase catalysing deamination = key regulatory point Allosterically - nucleotides (ATP, GTP or ADP, GDP) indicating energy status
Amino acid components (carbon skeleton, amino) sources
Nitrogen - mostly from glutamine/glutamate
Carbon skeletons - intermediates of glycolysis, pentose phosphate pathway, CAC
Different AA synthesis?
Depends on complexity of molecule and whether it is essential (usually more complex)
6 pathways of amino acid biosynthesis?
Grouped based on intermediate they are formed from
a-ketoglutarate 3-phosphoglycerate Oxaloacetate Pyruvate Phosphoenolpyruvate and erythrose 4-phosphate Ribose 5-phosphate
Regulation of AA biosynthesis
Allosteric regulation
Feedback inhibition where end product blocks first step
Regulation; threonine – isoleucine
Isoleucine is an allosteric inhibitor of threonine dehydratase, blocking this pathway i.e. stopping its own synthesis from threonine
Regulation; glutamate to glutamine
Very popular pathway, used in nitrogen transport
7 allosteric inhibitors of glutamine synthetase
Regulation; aspartate
Branched pathway - nested feedbacl inhibition
Aspartokinase governs with 3 isoenzymes for aspartate – lysine, methionine or threonine
Each of which is allosterically inhibited by their end product
AAs as metabolic precursors
Hormones, alkaloids, antibiotics, coenzymes, NTs etc, usually through providing nitrogen
e. g. glycine contributes carbon for haem groups
e. g. purine ring formation
