WEEK 9 (Amino acid degradation and synthesis)

Question 1

What are Glucogenic amino acids?

Answer 1

Amino acids whose catabolism yields pyruvate or one of the intermediates of the TCA cycle

Question 2

What is the importance of Glucogenic amino acids?

Answer 2

The intermediates are substrates for GLUCONEOGENESIS so give rise to the net synthesis of glucose in the liver and kidney

Question 3

What are Ketogenic amino acids?

Answer 3

Amino acids whose catabolism yields either acetoacetate or one of its precursors (acetyl CoA or acetoacetyl CoA)

Question 4

Name the different Ketone bodies

Answer 4

• Acetoacetate
• 3-Hydroxybutyrate
• Acetone

Question 5

Describe how Asparagine is converted to Oxaloacetate

Answer 5

ASPARAGINE is hydrolysed by ASPARAGINASE -> Liberates ammonia and aspartate -> Aspartate loses its amino group by TRANSAMINATION to form Oxaloacetate

Question 6

Explain how Asparaginase is used to treat leukaemia

Answer 6

Some rapidly dividing leukemic cells are unable to synthesise sufficient asparagine to support their growth -> ASPARAGINASE which hydrolyses asparagine to aspartate can be administered systemically to treat leukaemia -> Asparaginase LOWERS the level of asparagine in the plasma which deprives cancer cells of a required nutrient

Question 7

Describe how Arginine, Proline, Glutamine and Histidine are degraded to form Oxaloacetate

Answer 7

Gluconeogenic amino acids ARGININE, PROLINE, GLUTAMINE and HISTIDINE are all degraded first to GLUTAMATE and then further to ALPHA-KETOGLUTARATE -> ALPHA-KETOGLUTARATE can be converted to OXALOACETATE which participates in gluconeogenesis

Question 8

Where are non-essential amino acids synthesised from?

Answer 8

Intermediates of metabolism

Question 9

How are Hydroxyproline and Hydroxylysine produced?

Answer 9

By posttranslational modification of their precursor amino acids

Question 10

Describe Phenylketonuria

Answer 10

Phenylketonuria is an autosomal recessive disease where the body cannot change Phenylalanine (an essential amino acid) into Tyrosine since there is a decrease in PHENYLALANINE HYDROXYLASE or TETRAHYDROBIOPTERIN (BH4) COFACTOR. It is caused by a mutated PAH gene.

SYMPTOMS:
- Light hair, eyes and skin
- Eczema-like rash
- Seizures
- Hyperactivity
- Unpleasant odour
- Intellectual
- Phenylketones in urine

DIAGNOSIS: Screening occurs 2-3 days after birth (normal at birth because of maternal enzyme during fetal life)

TREATMENT:
- Limited intake of protein their whole lives
- Special diet starting a few days after birth
- Babies must drink a special formula without phenylalanine

Question 11

What is Maternal PKU?

Answer 11

Lack of proper dietary therapy during pregnancy

SYMPTOMS IN INFANT:
- Microcephaly (small baby head)
- Intellectual disability
- Growth retardation
- Congenital heart defects

Question 12

Why is the brain the main organ affected by hyperphenylalaninemia?

Answer 12

The CNS damage in affected patients is caused by the elevated concentration of phenylalanine in brain tissue -> High blood levels of phenylalanine in PKU saturate the transport system across the blood brain barrier -> Causes inhibition of the cerebral uptake of other large neutral amino acids (e.g Tyrosine and Tryptophan)

Question 13

What is Malignant PKU?

Answer 13

Malignant PKU is due to Tetrahydrobiopterin deficiency caused by a deficiency in DIHYDROPTERIDINE REDUCTASE

EFFECTS:
- HYPERPHENYLALANINEMIA due to decrease in conversion of phenylalanine to tyrosine -> decrease in synthesis of catecholamines
- Decrease in synthesis of Serotonin -> deficiencies of neurotransmitters

Question 14

Describe Alkaptonuria-Ochronosis

Answer 14

Alkaptonuria-Ochronosis is caused by HOMOGENTISIC ACID OXIDASE deficiency which results in the accumulation of HOMOGENTISIC ACID which polymerises to form ALKAPTONE BODIES

SYMPTOMS:
- Dark urine
- Arthritis
- Black pigment in cartilage & joints
- Classic X-ray finding = Calcification intervertebral discs
- Urine discolouration in infancy

DIAGNOSIS: Elevated HGA in urine & plasma

TREATMENT: Dietary restriction (Tyrosine & Phenylalanine)

Question 15

What are the three steps in the metabolism of branched chain amino acids

Answer 15

1) TRANSAMINATION
[enzyme = branched chain amino acid transaminase, coenzyme = PLP]
2) OXIDATIVE DECARBOXYLATION
[enzyme = branched chain kept acid dehydrogenase, coenzyme = Thiamine Pyrophosphate, FAD, NAD+, Lipomide and CoA]
3) DEHYDROGENATION
[enzyme = Acyl CoA Dehydrogenase, coenzyme = FAD]

Question 16

Describe Maple Syrup Urine Disease

Answer 16

Maple Syrup Urine Disease is a rare genetic metabolic disorder that occurs when the body cannot degrade BRANCHED CHAIN AMINO ACIDS causing a harmful, neurotoxic buildup of BCAA in blood and urine. Primarily due to the accumulation of LEUCINE.

[Classic MSUD occurs in the first few days of life]

SYMPTOMS:
- Lethargy and irritability
- Apnea
- Seizures
- Signs of cerebral edema

DIAGNOSIS:
- Elevated branched chain amino acid levels in plasma (Valine, Leucine & Isoleucine)

TREATMENT:
- Dietary restriction of branched-chain amino acids
- Monitoring plasma amino acid concentrations
- Thiamine supplementation

Question 17

Describe the degradation and resynthesis of methionine

Answer 17

Methionine condenses with ATP to form S-ADENOSYLMETHIONINE -> Methyl group is activated and transferred to oxygen, nitrogen and carbon atoms forming S-ADENOSYLHOMOCYSTEINE -> S-adenosylhomocysteine is hydrolysed to HOMOCYSTEINE -> Homocysteine is either remethylated to methionine (In methionine deficiency) or enters TRANSULFERATION PATHWAY to form CYSTEINE and KETOBUTYRATE which is oxidatively decarboxylated to form PROPIONYL COA which is then converted to SUCCINYL COA

Question 18

Describe Homocystinuria

Answer 18

An autosomal recessive disorder where there is too much HOMOCYSTEINE in the blood and urine

CAUSES:
- Cystathionine synthase deficiency (treatment: decrease methionine, increase cysteine, increase B6, B12 and folate in diet)
- Decreased affinity of cystathionine synthase for pyridoxal phosphate (treatment: increase B6 and cysteine in diet)
- Methionine synthase deficiency (treatment: increase methionine in diet)
- Methylenetetrahydrofolate reductase deficiency (treatment: increase folate in diet)

SYMPTOMS:
- Increased homocysteine in urine
- Osteoporosis
- Limited joint mobility
- Ocular lens dislocates downwards
- Heart attacks & strokes
- Kyphosis
- Intellectual disability
- Fair complex
- High arches of feet

Question 19

What is similar between Homocystinuria and Marfan syndrome?

Answer 19

• Long limbs
• Lens dislocation
• Scoliosis

Question 20

What are the symptoms of Marfan syndrome?

Answer 20

• Aortic dilation
• Aortic aneurysm
• Hyper flexibility
• Ocular lens dislocates upward
• Flat feet