WEEK 8 (Amino acid metabolism)

Question 1

What are amino acids?

Answer 1

Amino acids are organic compounds containing an AMINE GROUP, CARBOXYL GROUP, VARIABLE GROUP and a H ATOM around a central carbon atom

Question 2

What are the major key elements of amino acids?

Answer 2

• Carbon
• Hydrogen
• Nitrogen
• Oxygen

Question 3

Which amino acids are non-polar?

Answer 3

• Glycine
• Alanine
• Proline
• Valine
• Leucine
• Isoleucine
• Methionine
• Tryptophan
• Phenylalanine

Question 4

Which amino acids are polar and uncharged?

Answer 4

• Cysteine
• Asparagine
• Glutamine
• Serine
• Threonine
• Tyrosine

Question 5

Which amino acids are charged?

Answer 5

• Histidine
• Arginine
• Lysine
• Aspartate
• Glutamate

Question 6

What is the difference between Essential amino acids and Non-essential amino acids?

Answer 6

ESSENTIAL AMINO ACIDS = cannot be synthesised by the body -> must be consumed

NONESSENTIAL AMINO ACIDS = can be synthesised

Question 7

Which amino acids are essential?

Answer 7

• Leucine (KETOGENIC)
• Lysine (KETOGENIC)
• Phenylalanine (KETOGENIC/GLUCOGENIC)
• Isoleucine (KETOGENIC/GLUCOGENIC)
• Threonine (KETOGENIC/GLUCOGENIC)
• Tryptophan (KETOGENIC/GLUCOGENIC)
• Methionine (GLUCOGENIC)
• Valine (GLUCOGENIC)
• Arginine (GLUCOGENIC)
• Histidine (GLUCOGENIC)

Question 8

Which amino acids are nonessential?

Answer 8

• Alanine (GLUCOGENIC)
• Asparagine (GLUCOGENIC)
• Aspartate (GLUCOGENIC)
• Glutamate (GLUCOGENIC)
• Glutamine (GLUCOGENIC)
• Glycine (GLUCOGENIC)
• Proline (GLUCOGENIC)
• Serine (GLUCOGENIC)
• Cysteine (GLUCOGENIC)
• Tyrosine (KETOGENIC/GLUCOGENIC)

Question 9

What differentiates amino acids and proteins from fats and carbohydrates?

Answer 9

Unlike fats and carbohydrates, there is no storage form of amino acids and proteins so any excess/unused amino acids are broken down

Question 10

What happens in amino acid breakdown?

Answer 10

The amino group is removed forming NH3 + ALPHA-KETO ACID

Question 11

What are the properties of ammonia?

Answer 11

• Toxic to the body
• Needs to be transferred to LIVER in a NON-TOXIC STRUCTURE
• Converted by liver to UREA (non-toxic) for excretion by kidneys

Question 12

All amino acids except ________ and _________ participate in transamination at some point in their catabolism

Answer 12

Lysine and Threonine

Question 13

What are aminotransferases?

Answer 13

Transfer nitrogen from amino acids to glutamate

Question 14

What do all aminotransferases require?

Answer 14

The prosthetic group PYRIDOXAL PHOSPHATE (PLP) which is derived from PYRIDOXINE (VITAMIN B6)

Question 15

What is the clinical significance of Aminotransferases?

Answer 15

Aminotransferases are INTRACELLULAR ENZYMES with LOW LEVELS found in the plasma -> represents release of cellular contents during normal cell turnover -> ELEVATED PLASMA LEVELS of aminotransferases indicate DAMAGE to cells rich in these enzymes

Question 16

When are Plasma AST and ALT levels elevated in hepatic diseases?

Answer 16

In ALL hepatic diseases but particularly high in conditions that cause extensive cell necrosis

EXAMPLES:
- Severe viral hepatitis
- Toxic injury
- Prolonged circulatory collapse

Question 17

When are Aminotransferases elevated in non-hepatic diseases?

Answer 17

In diseases that cause damage to cardiac or skeletal muscle

Question 18

What are Oxidative deamination reactions and where do they occur?

Answer 18

Oxidative deamination reactions result in the liberation of the amino group as FREE AMMONIA and occur in the LIVER and KIDNEY

Question 19

What are the two mechanisms that are available for the transport of ammonia from peripheral cells to liver for detoxification?

Answer 19

• GLUTAMINE SYNTHETASE to combine glutamate with ammonia
• TRANSAMINATION of pyruvate to Alanine
  (used primarily by muscle)

Question 20

Describe transport of ammonia using Glutamine synthetase

Answer 20

GLUTAMINE SYNTHETASE combines ammonia with glutamate to form GLUTAMINE (nontoxic transport form of ammonia) -> GLUTAMINE is transported in blood to the LIVER where GLUTAMINASE cleaves it into GLUTAMATE and AMMONIA -> Glutamate is OXIDATIVELY DEAMINATED to ammonia and a-ketoglutarate by GDH

Question 21

Describe the transport of ammonia using Transamination

Answer 21

ALANINE is transported in the blood to the liver where it is TRANSAMINATED by ALT to PYRUVATE -> Glutamate product of ALT can be deaminated by GDH generating AMMONIA -> Both alanine and glutamine carry ammonia to the liver

Question 22

What are the properties of the Urea cycle?

Answer 22

• Occurs only in liver
• Toxic ammonia (urea) is excreted in urine
• Urea is synthesised from AMMONIA, CO2 and ASPARTATE

Question 23

What is the first stage of amino acid breakdown?

Answer 23

Removal of nitrogen by TRANSAMINATION [NH2 group is accepted by a-ketoglutarate forming GLUTAMATE]

Question 24

What are the properties of N-acetylglutamate?

Answer 24

• Regulates UREA CYCLE
• In the 1st step, N-ACETYLGLUTAMATE is an allosteric activator of CARBAMOYL PHOSPHATE SYNTHETASE I
• Synthesised from glutamate and acetyl CoA

Question 25

Glutamate and ammonia exist in a chemical equilibrium with glutamine, mediated by which enzyme?

Answer 25

GLUTAMINE SYNTHETASE

Question 26

Glutamate serves as a substrate for glutamate decarboxylase to form _______

Answer 26

GABA [This mechanism controls GABA concentration and GABAergic tone]

Question 27

What is Hyperammonemia?

Answer 27

Hyperammonemia is a metabolic condition characterised by the raised levels of ammonia Elevated serum ammonia levels disrupt the balance between GLUTAMINE, GLUTAMATE, A-KETOGLUTARATE and GABA through the actions of GLUTAMATE DEHYDROGENASE and GLUTAMINE SYNTHETASE -> Results in INCREASED GLUTAMINE and DECREASED GLUTAMATE levels -> low GABA synthesis and GABAergic tone TYPICAL FEATURES OF HYPERAMMONEMIC ENCEPHALOPATHY: - Excess glutamine -> Osmotic damage to ASTROCYTES -> Cellular swelling and dysfunction -> CEREBRAL EDEMA - Imbalance of neurotransmitters -> INHIBITION of excitatory neurotransmission and ACTIVATION of inhibitory neurotransmission - Low A-KETOGLUTARATE -> Inhibition of TCA cycle SYMPTOMS: - Flapping tremor (ASTERIXIS - inability to maintain sustained posture with brief, shock-like, involuntary movements) - Slurring of speech - Vomiting - Somnolence (drowsiness) - Vomiting - Blurring of vision - Can progress to coma

Question 28

Where are brief, low frequency, rhythmless tremor of the hand that occurs when the arm is outstretched and the wrist is extended seen most commonly?

Answer 28

Hepatic Encephalopathy

Question 29

What is Ornithine Transcarbamylase (OTC) deficiency?

Answer 29

Ornithine Transcarbamylase deficiency is the most common, X-linked recessive Urea cycle disorder which interferes with the body's ability to eliminate ammonia. Excess CARBAMOYL PHOSPHATE is converted to OROTIC ACID (part of pyrimidine synthesis pathway). (OTC deficiency is often evident in the first few days but may present later) EFFECTS: - Increased orotic acid in blood & urine - Decreased BUN (Blood Urea Nitrogen) - Symptoms of Hyperammonemia SYMPTOMS: - Cerebral edema - Lethargy - Convulsions - Coma - Death

Question 30

Describe Orotic Aciduria

Answer 30

Orotic Aciduria is the inability to convert OROTIC ACID to UMP (used in de novo pyrimidine synthesis pathway) because of defect in UMP SYNTHASE. Autosomal recessive. SYMPTOMS: Presents in children as - Failure to thrive - Developmental delay - Megaloblastic anemia resistant to FOLATE and B12 - No hyperammonemia

Question 31

Describe Orotic Aciduria

Answer 31

Orotic Aciduria is the inability to convert OROTIC ACID to UMP (used in de novo pyrimidine synthesis pathway) because of defect in UMP SYNTHASE. Autosomal recessive. SYMPTOMS: Presents in children as - Failure to thrive - Developmental delay - Megaloblastic anemia resistant to FOLATE and B12 - No hyperammonemia

Question 32

Describe Carbamoyl Phosphate Deficiency

Answer 32

Carbaryl Phosphate Deficiency is an autosomal recessive deficiency that does not produce orotic acuduria and causes ammonia to accumulate in the blood (hyperammonemia). [Least common deficiency of the urea cycle] EFFECTS: - Increase in ammonia (hyperammonemia) - Blood glutamine is increased - BUN is decreased - No OROTIC ACIDURIA SYMPTOMS: - Cerebral edema - Lethargy - Convulsions - Coma - Death