What cofactors are involved in metabolizing glycine to other substrates?
What cofactors are involved in metabolizing gluatmate to other substrates?
Describe the pathway of catecholamine synthesis.
1. Phenylalanine --> Tyrosine (via phenylalanine hydroxylase); 2. Tyrosine --> dihydroxyphenylalanine (aka Dopa) (via tyrosine hydroxylase); 3. dopa --> dopamine (via dopa decarboxylase and requiring B6); 4. dopamine --> norepinephrine (via dopamine-b-hydroxylase and requiring vitamin C); 5. Norepinephrine --> epinephrine (via phenylethanolamine N-methyltransferase and requiring SAM) (p.108)
What enzyme does carbidopa inhibit?
Dopa decarboxylase, preventing synthesis of dopamine from dopa (p.108)
What is the effect of cortisol on norepinephrine?
Induces conversion to epinephrine (p.108)
What is the function of SAM?
To add a methyl group to a substrate (p.108)
What is the breakdown product of dopamine via MAO and COMT?
What is the breakdown product of norepinephrine via MAO and COMT?
What is the breakdown product of epinephrine via MAO and COMT?
What is the pathology associated with phenylketonuria?
Caused by decreased phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor (malignant PKU). Increased phenylalanine causes excess phenylketones (phenylacetate, phenyllactate, phenylpyruvate) in urine and makes tyrosine an essential amino acid (p.108)
What is the pattern of inheritance associated with phenylketonuria?
An autosomal recessive condition with incidence about 1:10,000. It is screened for 2-3 days after birth (because it is nrmal at birth due to maternal enzyme during fetal life) (p.108)
What are the symptoms of phenylketonuria?
Mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor (p.108)
What is the treatment for phenylketonuria?
Decrease phenylalanine in diet (contained in aspartame) and increase tyrosine in diet (p.108)
What is maternal PKU?
Lack of proper dietary therapy during pregnancy causes an infact to have microcephaly, mental retardation, growth retardation, and congenital heart defects (p.108)
What is alkaptonuria (ochronosis)?
A congenital deficiency of homogentistic acid oxidase in the degredative pathyway of tyrosine to fumarate. It is a benign disease (p.108)
What is the inheritance pattern associated with alkaptonuria?
Autosomal recessive (p.108)
What are the clinical findings in a patient with alkaptonuria?
Dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. May have debilitating arthralgias as homogentisic acid is toxic to cartilage (p.108)
What is the pathology associated with albinism?
A congenital deficiency of either tyrosinase (inability to synthesize melanin from tyrosine) or due to defective tyrosine transporters which decrease the amount of tyrosine and thus melanin. It can also result from a lack of migration of neural crest cells. (p.108)
What is the inheritance pattern associated with albinism?
Can be autosomal recessive but inheritance is variable due to locus heterogeneity (p.108)
What is the pattern of inheritance of occular albinism?
X-linked recessive (p.108)
Describe the three pathologies that may lead to homocystinuria.
1.) Cystathionine synthase deficiency; 2.) Decreased affinity of cystathionine synthase for pyridoxal phosphate; 3.) Homocysteine methyltransferase (requires B12) deficiency (p.109)
What is the pattern of inheritance in homocystinuria?
All three types are autosomal recessive (p.109)
How do you treat homocystinuria associated with a cystathionine synthase deficiency?
Decrease methionine and increase cysteine, Vitamin B12, and folate in the diet (p.109)
How do you treat homocystinuria associated with a decreased affinity of cystathionine synthase for pyridoxal phosphate?
Increase vitamin B6 in diet (p.109)
Describe the clinical and lab findings in a patient with homocystinuria.
All forms of homocystinuria result in excess homocysteine amd makes cysteine essential. Findings include increased homocysteine in the urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downwards and inwards), and atherosclerosis (stroke and MI) (p.109)