Amino Acid Metabolism Flashcards
1
Q
Describe proteins
A
- Raw material for amino acids
- Carbon, Oxygen and Nitrogen (16% by weight)
- Can be used to form ATP
2
Q
What can proteins be broken down and reassembled to form?
A
- Muscle protein
- enzymes,
- Structural proteins
- Membrane channels and pump
- Immunity
- Hormones
3
Q
Describe amino acids in the fed state (liver)
A
- Liver to synthesise hepatic and serum proteins, biosynthesis of N-containing proteins like haem, hormones, purine/ pyramiding bases
4
Q
What is excess amino acid converted to?
A
- Glycogen
- Or triacylglycerol
5
Q
What is the function of broken down amino acids in the peripheral circulation?
A
- Periphery for protein synthesis, biosynthetic pathways and oxidation
- Low carb and fat diet–> AA used for ATP source
6
Q
What happens to amino acids in the basal state?
A
- Recycling of AA not needed
- Glucose/ ketone body synthesis
- Urea synthesis needed for AA breakdown- allows safe removal of N
- Amino acids used as C source for gluconeogenesis
- Muscle protein preferentially degraded
7
Q
What is urea?
A
- Very soluble, non-toxic nitrogen containing substance that is readily excreted by the kidneys
8
Q
What happens to amino acids in the prolonged fasting state?
A
- Similar to basal
- Spare use of muscle protein to maintain health
- Switch to ketone bodies, less reliance on glucose to spare AA
9
Q
What is transamination?
A
- Funnelling of nitrogen-containing amino group from an amino acid to an acceptor
10
Q
What is transamination essential for?
A
- Degradation of most amino acids
- Synthesis of non-essential amino acids
- Exchange amino groups between amino acids
11
Q
Describe what is happening in a transamination reaction
A
- Swaps amino group to a different keto acid
- Generates a new pair of AA and keto acid
- Readily reversible
- AA usually glutamate and corresponding keto acid is α-glutamate
12
Q
What enzyme facilitates transamination?
A
- Aminotransferase (or transaminase enzymes)
- Different for different amino acid substrates
- (E.g. alanine aminotransferase)
13
Q
Give two examples of transamination reactions
A
1) Alanine –> Pyruvate
- α-ketoglutarate–> glutamate
- Alanine aminotransferase
2) Oxaloacetate –> Aspartate
- Glutamate–> α-ketoglutarate
- Aspartate aminotransferase
- -> Both reactions are reversible
14
Q
How does glutamate incorporate into the urea cycle?
A
- Glutamate or aspartate
- N can only be incorporated into urea cycle via those two
- Glutamate releases ammonia via carbamoyl phosphate (enters cycle)- oxidative deamination
- Regenerates α-ketoglutarate
15
Q
How does aspartate incorporate into the urea cycle?
A
- Combines with citrulline
16
Q
Where does the urea cycle occur and what does it do?
A
- Liver
- Converts nitrogen into urea for excretion by the kidneys
17
Q
How do other amino acids incorporate themselves in the urea cycle?
A
- Transamination passing amino groups to α-ketoglutarate or oxoaloacetate to produce glutamate and aspartate
- They become keto acids that can be used in gluconeogenesis
18
Q
What happens in oxidative deamination?
A
- NAD–> NADH
- Glutamate –> amino + α- ketoglutarate
- Ammonia becomes carbamoyl phosphate
- Enzyme condenses ornithine and carbamoyl phosphate producing citrulline
- Citrulline condenses with aspartate –> arginosuccinate–> Arginine + fumarate
- Arginine–> ornithine + urea
- Fumarate can be converted to oxaloacetate to join TCA cycle
19
Q
What enzyme condenses carbonyl phosphate and ornithine in the urea cycle?
A
ornithine transcarbomaoylase (OTC)
20
Q
What enzyme converts glutamate into ammonia?
A
glutamate dehydrogenase
21
Q
What is meant by nitrogen balance?
A
– Any normal healthy adult will ingest and secrete same amount of nitrogen, maintain nitrogen balance
22
Q
What is positive nitrogen balance?
A
- Taking in more nitrogen
- Need to increase protein synthesis (after accident, pregnancy, rapidly growing baby)
- Not excreting same amount nitrogen as taken in
23
Q
What is negative nitrogen balance?
A
- Muscle protein/ haemoglobin degraded to provide N for synthesis of other proteins
- Needing to use up excess N
- Amount of N excreted more than ingested, no amino acids ingested
- Urea created when amino acids metabolised
24
Q
What is hyperammonaemia?
A
- Accumulated toxic NH₄⁺ travels- brain (coma, damage and death)
- Causes: hepatocyte loss (e.g. liver cirrhosis) or urea cycle enzyme deficiency
25
What enzyme in the urea cycle is more likely to be deficient leading to hyperammonaemia?
- Orthenine transcarbamoylase
- Mutant enzyme protein impairs reaction and condenses carbonyl phosphate + ornithine to form citrulline
- X-linked gene, high male mortality
- Treatment is low protein diet or liver transplant
26
Describe Alanine in inter-organ C and N shuttle
- Simplest AA- muscle protein
- Simplest transport method
- Amino groups from broken down AA passed onto pyruvate to produce alanine
- C shuffles in blood as alanine- converted back to pyruvate in liver
- Glutamate transfers N into urea cycle (oxidative de-am.)
- Meanwhile, pyruvate enters gluconeogenesis
27
What enzyme is used to convert alanine to pyruvate?
- Alanine transaminase (ALT)
| - This enzyme is also elevated (released) during liver damage
28
What is meant by the term carbon skeletons?
- AA broken down, amino group shuffled by either aspartate or glutamate into urea cycle- remains= carbon skeleton
- Can be integrated into TCA cycle
29
What are glucogenic amino acids?
- Carbon skeletons of AA used to produce glucose through gluconeogenesis
- Mostly resemble different things in TCA cycle (e.g. alanine, cysteine etc similar to pyruvate)
30
What are ketogenic amino acids?
- Carbon skeletons degraded to form acetyl CoA- metabolised immediate precursors to lipid or ketone bodies
- Mostly resemble acetyl CoA
31
What are the possible fates of carbon skeleton?
- Depends on physiological state and tissue
- Fasting- converted to glucose or ketone bodies released in blood as fuel
- Fed- converted to fuel such as glycogen/ triacylglycerols (only in liver)
- If tissue needs energy- oxidised to produce ATP via TCA cycle
- Precursors to synthesise other proteins needed by cells
32
What are the metabolic relationships among amino acids?
- Make body proteins, which can also break down--> AA
- Ingested broken down to get constituent AA
- Used as fuel source:
- - Urea cycle
- - Acetyl CoA make ketone bodies/ other fats
- - Glucose- glycolysis
- - Ketone bodies- β- oxidation
33
What other things can amino acids be converted to?
- Purines and pyrimidines
- Porphyrins
- Thyroxine
- Neurotransmitters
- Phospholipids
- Coenzymes
34
What clinical consequences of errors in amino acid metabolism are there?
- Phenylketonuria
- Albinism
- Alkaptonuria
- Maple Syrup Urine Disease (MSUD)
35
Describe what happens in phenylketonuria (PKU)
- phenylalanine--> tyrosine--> melanin (normal)
- phenylalanine hydroxylase not functional
- Phenylalanine degrades
- Detected by increased serum phenylalanine and excess urinary excretion of phenylpyruvate & phenylactate
- Early detection & treatment- protein restricted diet and tyrosine supplement avoid severe mental retardation
- Autosomal recessive
36
Describe what happens in albinism
- Autosomal recessive
- Tyrosine--> melanin (normal)
- Tyrosinase mutation- lack melanin pigment
- Skin, hair and eyes hypo pigmented
- UV vulnerability, increased cancer risk
- Visual problems
- No cure, complications managed by dermatology/ ophthalmology
37
Describe what happens in Maple Syrup Urine Disease (MSUD)
- Absent α-ketoacid dehydrogenase- build up of α-ketoacids
- Specific to valine, leucine and isoleucine metabolism
- May develop 4-7 days after birth- lethargy, weight loss, metabolic derangement, progressive neurologic signs of altering hypo/hypertonia- severe encephalopathy
- Seizures and comas possible
- Death possible
- Autosomal recessive
