Amino Acid Metabolism

describe the fate of the carbon core of Amino Acids

depends on state of energy

fed state: creation of glycogen and triglycerides

Fasting state: TCA intermediates, pyruvate, acetyl-CoA, acetoacetate, CO2

In both: makes physiologically important metabolites

What organ can degrade all amino acids?; draw out the summary of the degradation of amino acids

liver;

Draw out the chart classifying nonessential, conditionally essential and essential for glugogenic, glucogenic/ketogenic and ketogenic

outline the synthesis of nonessential amino acids

list out the cofactor in AA metabolism, its vitamin, and typical enzymatic reactions in context of AA metabolism

Draw out the pathway for AA that are degraded to OAA; Why is asparaginse use as an antileukemic drug?

Draw out the pathway for AA that are degraded to a-ketoglutarate

Draw out the pathway for histidine metabolim; What does histamine do? What is histidinemia? What do patients with folic acid deficiency excrete in surplus?

Draw out the pathway for Amino Acids degradation to Pyruvate. What is the primary reaction that produces glycine in the brain?

Draw out the glycine degradation pathway and the two diseases that could arrise from this.

Describe the pathway of making homocystein

What is the primary methyl donor in the body and what does it participate in the syntehsis of?

SAM (s-adenoylmethonine)

participate in:

1. phosphatidyl choline (cell membrane lipid)

2. creatine (muscle energy metabolism)

3. melatonin

4. epinephrine

draw out the pathway for degradation of homocystein

What is homocystinuria? Symptoms?

What is cystathioninuria? Symptoms?

what is high levels of homocystein a risk factor of? How is it treated

high levels of homocystein = risk factor for myocardial infarction; management = restrict methionine, supplement cysteine

draw out the chart describing how cystathionase, cystathionine synthase deficiency and B12 deficiency affect blood levels of methionine, homocystine and cystathionine

What are symptoms and treatment of Homocystinuria?

Symptoms:

• elevated homocystine levels in blood/urine

• intellectual disability or developmental delay

• ectopia lentis (dislocated lens)

• skeletal abnormalities (marfan-like)

• increased risk of myocarial infarction

treatments:

1. dietary restriction of Met, and supplementation of Cys

2. Vitamine B6 supplementation if responsive

3. Vitamine B12 and folic acid supplementation if responsive

4. betaine supplementation (methylation of homocysteine)

Draw out the pathway for degradation of Amino Acids to Succinyl CoA

Differentiate between methylmalonic acidemia an propionic acidemia

methylmalonic acidemia:

1. methylmalonhyl CoA mutase deficiency

2. elevated levels of methyl-malonyl acid occur in blood

3. metabolic acidosis and developmental problems occur

Propionic aciemia

1. due to deficiency in propinyl-CoA carboxylase

2. elevated levels of 3-OH propionic acid

3. metabolic acidosis

these diseases are known as organic acidemias and lead to secondary hyperammonemia

draw out the pathway for AA degradation to fumarate

Describe tyrosinemia Type 1

• deficiency in fumarylacetoacetate hydrolase

• accumulation of fumarylacetoacetate in hepatocyte

  • hepatic failure, jaundice, cirrhosis, hepatocarcinoma and failure to thrive; associated with very high alph-fetoprotein

• accumulation of succinyl-acetone in blood/urine → kidney failure

  • high excretion of phosphate in urine → rickets (low bone density)

• Elevated plasma levels of phenylalanine, tyrosin, and methionine

• elevated urine aminolevulinic acid levels

  • inhibition of heme synthesis and neurological crisess similar to acute intermittent poryphria

    • change in mental status, abdominal pain, respiratory failure

• characteristic cabbage-like odor occurs

• liver failure and renal tubular aciosis

• treatment: dietary restriction of phenylalanine and tyrosine.

draw out the important metabolites of tyrosine

What is oculocutaneous albinism type 1

• due to tyrosinase deficiency

• white skin, white hair, pink eyes

• eye and skin ssensitive to sunlight

• nystagmus, far or near sightedness

what is alkaptonuria? discuss this disease’s effect on the urine, eyes, and vertebrae

• disease of the tyrosine degraation pathway

• due to homogentistic acid oxidase deficiency

• homogentistic acid accumulates in urine and tissues

• accumulation in cartilate causes crippling arthritis

urine:

• after two hours of urine sample, it is entirely black ue to oxiation of homogentisic acid

Eyes:

• bluish-black pigmentation in teh sclera of the eye and in teh cartilage o the ear

vertegrae:

• dense, black pigment depositied on the intervertebral disk

Describe phenylketonuria (PKU)

• due to phenylalanine hydroxylase deficiency

  • mutation in enzyme or insufficient tetrahydrobiopterin (BH4)

• Symptoms:

  • elevated phenylalanine, phenylpyruvate, phenyllactate, and phenylacetate in blood and urine = musty odor in urine

  • neurological problems (meental rtardation ,seizurse, tremor, microcephaly, etc) due to reduced production of catecholamins

  • hypopigmentation due to reduced melanin production

• tratment: phe-restricted, tyr-supplemented diet. avoid aspartame, artificial sweetner

• neonatal screening is mandatory

What is BH4 necessary in hydroxylation of? why is BH4 deficiency cause mor severe PKU than mutation in phenylalanine hydroxylase?

phenylalanine (tyrosine production)

tyrosine (first step of catecholamine synthesis)

tryptophan (first step of serotonin and melatonin synthesis)

More severe because more pathway inhibited

draw out the pathway for Branched-Chain amino Acid degradation

Describe MSUD

• Maple Syrup Urine Disease

• due to deficient a-keto dehydrognas

Symptoms/lab result

• elevated branched chain amino acids (BCAAs) especially leucine in blood

• elevated branched chain ketoacids (BCKA) in blood and especially in urine

• BCKA causes maple syrup odor of urine and of earwax

• encephalopathy (lethargy, poor feeding, apnea, opisthotonus, coma)

Management:

• BCAA restricted high calorie diet: usually BCAA-free formulas, supplmented with limited amounts of BCAAs. Leucine is always the most restricted. (all BCAAs are essential amino acid)

draw out the pathway for metabolism of tryptophan

What is pellagra and what are its symptoms?

lack of tryptophan and niacin (vitamin B3) in diet causes pellagra

characterized by 4ds

1. dermatitis

2. diarrhea

3. dementia

4. death (if untreated)