Amino Acids- clinical correlates-Brar

Question 1

deficiency in glycine cleaving enzyme

Answer 1

Glycine degradation carried out by glycine cleaving enzyme
Important source of one carbon units for tetrahydrofolate
Deficiency in enzyme causes nonketotic hyperglycinemia
Rare, recessively inherited disease (1 in 250,000 infants)
Causes death infancy or profound mental retardation in survivors
Glycine can also be converted into oxalate which is found in most kidney stones

Question 2

Deficiency in cystathionine synthase

Answer 2

Leads to accumulation of homocysteine and methionine
Causes thinning and lengthening of bones
Osteoporosis
Lens dislocation
Tendency for vascular thrombosis
Incidence is about 1 per 200,000 patients
Recessively inherited condition
Treated by restricting dietary methionine and adding folic acid supplements
Vitamin B6 and B12 are also sometimes effective
These are cofactors for the homocysteine metabolizing enzymes
High levels of homocysteine in a risk factor cardiovascular disease

Question 3

Maple Syrup Urine Disease

Answer 3

Disorder of branched chain amino acid degradation
Deficiency of branched chain  keto acid dehydrogenase
Complete deficiency leads to
Severe mental retardation
Acidosis
Sweet odor to urine
Early death
Thiamine supplement is sometimes useful
Dietary restriction of valine, leucine and isoleucine is not always successful

Question 4

Phenylketonuria

Answer 4

Classical disease caused by complete lack of phenylalanine hydroxylase
Raises phenylalanine levels by almost 10 fold
Urine contains mostly phenylpyruvate
No abnormalities at birth because phenylalanine and metabolites are transferable across placenta

Untreated disease causes mental retardation, seizures, spasticity and other neurological symptoms
Patients also have a light complexion compared to unaffected siblings (Why?) PKU can be treated by severely restricting dietary phenylalanine
can’t completely eliminate from diet because need some phenylalanine for other tissue proeteins, catechoalamines, melanin and fumarate acetoacetate
Only the developing brain is vulnerable to PK–> diet can be tapered off in adolescence.
Aspartame is also hazardous to patient.
PKU screening is mandatory in the US

Question 5

Essential amino acids

Answer 5

must be obtained in diet.
Valine
Threonine
Leucine
Methionine
Isoleucine
Lysine
Phenylalanine
Histidine
Tryptophan

Question 6

Glucogenic Amino Acids

Answer 6

Glucogenic amino acids are those that give rise to a net production of pyruvate or TCA cycle intermediates –>precursors to glucose via gluconeogenesis

All amino acids except lysine and leucine are at least partly glucogenic

Question 7

Ketogenic Amino Acids

Answer 7

Lysine and leucine are the only amino acids that are solely ketogenic, giving rise only to acetylCoA or acetoacetylCoA, neither of which can bring about net glucose production

Question 8

Dual Use Amino Acids

Answer 8

A small group of amino acids (isoleucine, phenylalanine, threonine, tryptophan, and tyrosine) give rise to both glucose and fatty acid precursors and are thus glucogenic and ketogenic