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85 Cards in this Set
- Front
- Back
What is amino acid metabolism?
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Protein break down through sequential enzyme digestion
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What is a protease?
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Enzyme that catalyses the hydrolytic breakdown (hydrolysis - chemical breakdown due to reaction with water) of proteins into peptides or amino acids (proteolysis)
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What is an endopeptidase?
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An enzyme that breaks peptide bonds other than terminal ones in a peptide chain
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What is an exopeptidase?
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A peptidase that catalyses the removal of the last (carboxypeptidases) or first (aminopeptidases) amino acid from a peptide chain.
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What enzyme does the stomach secrete?
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Pepsin (an endopeptidase) in its inactive form (zymogen) pepsinogen
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How is pepsinogen activated?
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Cleavage (by HCl) of a peptide fragment from its amino terminus
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When does this activation occur?
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Autoactivated by active pepsin
Also, when pH of stomach lumen <5 - acidity denatures proteins so they are more susceptible to hydrolysis |
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What are serine proteases(/endopeptidases)?
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Enzymes that cleave peptide bonds in proteins in which serine is one of the amino acids in the enzyme's active site.
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What enzymes does the pancreas secrete?
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Serine endopeptidases - Trypsin, chymotrypsin and elastase.
Exopeptidases - carboxypeptidases A&B |
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Where do these enzymes act?
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Work in the lumen of the small intestine
Neutral conditions due to secretion of bicarbonate rich pancreatic juice |
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In what form are all pancreatic proteases secreted in?
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Inactive precursors - (trypsinogen, chymotrypsinogen, proelastase, procarboxypeptidase A&B)
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How is trypsinogen activated?
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By enteropeptidase (also called enterokinase)
By active trypsin (autocatalytic process) |
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What releases enteropeptidase?
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Secreted from enterocytes (the epithelial cells of the small intestine)
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How are the other inactive precursors secreted by the pancreas activated?
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Cleavage with trypsin
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What is left after digestion by pancreatic enzymes?
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Mix of amino acids and small peptides up to 6 amino acids long (oligopeptides)
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Diseases which interfere with pancreatic secretion... (2) - associated problems
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Pancreatitis and CFTR - prevent proper protein digestion resulting in protein malabsorption leading to malnutrition
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What is the treatment for reduced pancreatic secretion?
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Supply either extra exogenous pancreatic enzymes or dietary supplements of easily digested proteins
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After pancreas where do digestive enzymes come from and at?
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Brush-border membrane of enterocytes
Lumen of small intestine |
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What enzymes does the brush-border contain?
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Endopeptidases, aminopeptidases and dipeptidases
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After brush-border enzyme digestion, what is left?
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Mixture of dipeptides, tripeptides and amino acids
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What takes up di- and tripeptides into enterocytes?
CLINICAL: What else is this transporter responsible for? |
Proton-coupled transporter
Absorption of beta-lactam antibiotics |
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What absorbs amino acids into enterocytes?
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A number of mainly sodium-coupled transport systems
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What happens to di- and tripeptides once in enterocytes?
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Cleaved by intracellular peptidases into free amino acids
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What happens to amino acids in enterocytes?
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Released via the basolateral membrane and enter the circulation
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What are essential amino acids? Name them
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Those that the body cannot make - alanine, aspartate, asparagine, cysteine, glutamate, glutamine, glycine, prolein, serine and tyrosine.
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Uses of amino acids
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Protein synthesis, hormone production e.g. adrenaline, neurotransmitter synthesis.
Deaminated - remaining carbon skeleton can then be either oxidised via TCA cycle, converted into glucose via gluconeogenesis or turned into fatty acids (not all are capable of all these fates) |
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Which amino acids are glucogenic?
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Those which can be degraded to pyruvate or TCA cycle intermediates
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Which amino acids are ketogenic?
Name the two which are solely ketogenic |
Those which are convert into acteyl-CoA or acetoacetyl-CoA
Leucine and lysine |
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What is the term for amino acids which are both gluco and ketogenic?
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Mixed
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Points of entry of amino-acid carbon skeletons into the citric acid cycle and into ketone body synthesis...
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Where are excess amino acids stored?
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They cannot be stored
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First step of amino acid oxidation
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Remove amino group (deamination) - excreted as urea
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How is the amino group removed?
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Transamination - catalysed by aminotransferases (transaminases)
Each amino acid has its own specific aminotransferase |
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What is the overall reaction for transamination?
Two features of the reaction |
Amine group of an amino acid and keto group of a keto acid are exchanged
Easily reversible, requires no energy input |
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What is the co-factor of all aminotransferases?
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Pyridoxal phosphate (vitamin B6 derivative)
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Most common amino group acceptor?
What does this form and how is the product used? |
Alpha-ketoglutarate
Glutamate - provides pool of amino groups for non-essential amino acid synthesis and deamination. |
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Two other amino group acceptors and what they form as a result
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Pyruvate --> alanine
Oxaloacetate --> aspartate |
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What deaminates glutamate
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Glutamate dehydrogenase
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What is the benefit of pooling excess amino groups into glutamate?
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Only one deamination pathway is required
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Overall deamination reaction and where it takes place
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Removal of amine group
Mitochondria of liver cells |
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Main fate of ammonium (NH4+) from deamination reaction?
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Incorporation into urea for excretion
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What allosterically regulates glutamate dehydrogenase and why?
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Increases in ADP and GDP - these compounds signal that amino acids need to be used as an energy source.
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Other sites of NH4+ production (3)
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Brain, muscle, intestinal cells
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How are ammonium ions produced in the brain?
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Inactivation (through breakdown) of neurotransmitter GABA into succinate and NH4+
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How do ammonium ions produced in the brain enter the urea cycle?
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One NH4+ combined with alpha-ketoglutarate to produce glutamate and then another incorporated to form glutamine --> transported to liver where it is deaminated and enters urea cycle
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How are ammonium ions produced in muscle? (3)
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Natural protein turnover
Muscle catabolism during starvation Breakdown of excess ADP during extreme exercise - 2ADP ----> ATP + IMP + NH4+ |
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What happens to the NH4+ produced in muscle?
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Combines with alpha-ketoglutarate to form glutamate - used to transaminate pyruvate, forming alanine and regenerating alpha-ketoglutarate.
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What is the fate of alanine produced from the transamination of pyruvate in muscle cells?
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Released into the bloodstream and taken up by the liver.
Deaminated, producing pyruvate which can either be oxidised in the TCA cycle or used for gluconeogenesis. |
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What happens to the NH4+ produced in intestinal cells (enterocytes)?
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Same as brain, NH4+ combined with alpha-ketoglutarate to produce glutamate and then another incorporated to form glutamine - this serves as an energy source for the cell.
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What are the two forms in which excess nitrogen can be excreted?
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Urea or ammonium ions
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Where in the body is urea generated and why?
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In the liver as a soluble, non-toxic way of eliminating excess ammonia
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What else can deaminate glutamate?
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The renal cortex
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How is ammonium used in the renal cortex?
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Ammonium is used to assist with acidifying urine.
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Why is the mechanism for deamination of glutamate in the renal cortex beneficial?
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Mechanism conserves HCO3- which would otherwise need to be used in urea synthesis - would exacerbate any acidosis.
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What happens if protein intake is greater than need?
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Cannot store excess amino acids - carbon skeletons are used/stored and unwanted amino groups are excreted.
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What happens if protein intake is less than need?
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Protein catabolism to free carbon skeletons for energy - the amino groups produced need to be excreted
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Why do blood ammonia levels need to be kept low?
What is the normal value? |
Toxic
(25-40 μM - micro molar) |
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What happens if ammonium ion levels rise?
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NH4+ reacts with alpha-ketoglutarate to form glutamate
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What are the consequences for the brain of raised NH4+ levels?
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Resulting raised glutamate levels reduce the rate at which ATP can be formed, starving brain cells of energy
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What is 'nitrogen balance'
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State of healthy adults - around 80% of excess nitrogen excreted as urea (remainder in free ammonium ions and creatine)
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Where is most urea synthesised? (Organ)
Why is rate of synthesis strictly controlled? |
In the periportal cells (those surrounding the portal vein) or the liver.
To prevent ammonia build up |
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The urea cycle
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Formation of urea from one free ammonium ion and one donated from aspartate
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Where does the urea cycle take place? (Cell)
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Partly in the mitochondrial matrix, partly in the cytoplasm
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What two amino acids does the urea cycle include that are not found in proteins?
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Ornithine and citrulline
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What are the two levels of urea cycle control?
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Acute and chronic
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What enzyme controls acute regulation of the urea cycle and what is this regulated by?
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Carbamoyl-phosphate synthetase is regulated by the concentration of the allosteric activator N-acetyl-glutamate
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What forms N-acetyl-glutamate and what stimulates this?
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N-acetyl-glutamate synthase - activity stimulated by arginine (intermediate of the urea cycle)
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What controls chronic regulation of the urea cycle? Time period?
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Induction of urea cycle enzymes over 24-36 hours
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What triggers chronic regulation?
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Increased levels of ammonia in liver cells
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What are the consequences for enzyme synthesis of prolonged or severe starvation?
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Amino acids deaminated to use carbon back bone for energy - this may cause protein (and so enzyme synthesis) to be compromised
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What is the treatment if control of the urea cycle is not functioning correctly?
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Reduce protein level in diet and give a compound which aids nitrogen excretion (either through stimulating urea cycle or another compensatory pathway)
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EXTRA What is the most common urea cycle disorder?
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Ornithine transcarbamoylase deficiency
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EXTRA Which gender is most severely affected by ornithine transcarbamoylase deficiency and why?
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Generally males because the disease is X-linked
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EXTRA What are the symptoms of ornithine transcarbamoylase deficiency and what do these cause?
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Raised ammonia and amino acid levels, high blood or ororatic acid levels.
Mental retardation and can cause dead. |
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EXTRA What is the treatment for ornithine transcarbamoylase deficiency and why?
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Large quantities of benzoate and phenylacetate:
Benzoly-CoA reacts with glycine to form hippurate Phenylacetyl-CoA reacts with glutamine to form phenylacetylgluatime These products act as excretable substitutes for urea in the disposal of nitrogen. |
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Which organ is the main site of deamination (amino acid degradation) and urea synthesis?
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The liver
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Which organ is the main site of gluconeogenesis during fasting? What fuels this process?
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The liver
Carbon skeletons from amino acids |
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What is the function of glutamate reductase?
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Synthetic enzyme for citrulline
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Which are the only cells to contain glutamate reductase?
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Enterocytes
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What is the fate of citrulline produced in the gut?
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Metabolised to arginine in the liver - this is then converted to ornithine to increase the capacity of the urea cycle during times of increased protein intake.
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What happens to muscle protein during fasting and starvation?
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Broken down to provide carbon skeletons for gluconeogenesis in the liver
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What are the main amino acids released from muscle protein breakdown?
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Alanine and glutamine
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What is the fate of alanine released from muscle protein catabolism?
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Transported by the circulation to the liver for deamination and gluconeogenesis
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What is the fate of glutamine released from muscle protein catabolism?
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Transported to small intestine by circulation, taken up by enterocytes for energy and released as alanine
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Glucose-alanine cycle
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Transport nitrogen to liver as alanine and glucose back to muscles
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