Amino Acid Metabolism

Front 1

Outline the hydrolysis of dietary amino acids

Back 1

Ingested protein rich food is first digested into peptides in the stomach by pepsin

Peptides are digested further into amino acids in the small intestines by trypsin, chymotrypsin, proelastase, aminopeptidases and procarboxypeptidases

Front 2

Outline the absorption of dietary amino acids

Back 2

Amino acids are absorbed into the epithelial cells of the brush border via co-transport with Na⁺

Amino acids then enter the portal vein via facilitated transport out of the epithelial cell

Front 3

Hartnup Disease

Back 3

Defective transport in the kidney and intestines of large, neutral amino acids

- especially tryptophan

Marked amino acid loss through urine excretion

Often associated with pellagra-like symptoms

- vitamin deficiency associated with lack of B3

Front 4

Outline the urea cycle

Back 4

5 step process

- first two = mitochondria

- last three = cytosol

1. NH₄⁺ → Carbamoyl Phosphate

- Carbamoyl Phosphate Synthase I (CPS I)

- requires 2 ATP

2. Carbamoyl Phosphate + Ornithine → Citruline

- Ornithine Transcarbamylase

3. Citruline + Aspartate → Arginosuccinate

- Arginosuccinate Synthase

- requires ATP

4. Arginosuccinate → Arginine + Fumarate

- Arginosuccinate Lyase

5. Arginine → Ornithine + Urea

- Arginase

Front 5

Define the biochemical process of transamination

Back 5

The transfer of amino groups between molecules

Most conserved way to handle N in rxns

Requires a co-factor

- typically pyridoxal phosphate

Common transaminases = alanine transaminase and glutamine transaminase

Front 6

Amino Acid Sources for the Urea Cycle

Back 6

Amino acids can feed into the urea cycle from

- the brain

- skeletal muscle

- the gut

- denovo synthesis within other cells

Front 7

Ornithine Transcarbamylase Deficiency

Back 7

Affects 1:80,000

Elevated blood ammonia levels and orotic acid

If untreated, leads to mental impairment

Reduce dietary arginine or undergo ERT

Front 8

Glutamate

Back 8

Central AA metabolite

Converted to glutamine in peripheral tissues

- allows the transport of NH₄⁺ to the liver for entry into the urea cycle

- glutamate + H2O + NADP+ → α-ketoglutarate + NADPH + NH3 + H+

Acts as an intermediate in the synthesis of non-essential amino acids

Aspartate + α-ketoglutarate ⇌ oxaloacetate + glutamate

Front 9

Alanine Metabolism

Back 9

Conversion to glucose and urea requires glutamate

Alanine + α-ketoglutarate ⇌ pyruvate + glutamate

- pyruvate can then go on to form glucose through gluconeogenesis

Front 10

Phenylketonuria

(PKU)

Back 10

Defect in phenylalanine hydroxylase leads to buildup of excess phenylalanine in blood

Phenylalanine is then converted to phenylpyruvic acid

Treated by reductions in dietary phenylalanine

If not treated can lead to

- mental retardation

- microcephaly

- musty odor

Front 11

Albinism

Back 11

Blockage of melanin synthesis from tyrosine

Characterized by white hair, pale skin, and translucent irises

Increased risk for skin cancer

Front 12

Alcaptonuria

Back 12

Age of onset >30

Dark, black urine

Ochrinosis

- blue coloration of cartilaginous tissue

Treatment

- low protein diet

- nitisinone

Front 13

Maple Syrup Urine Disease

Back 13

Inability to metabolize branched chain AAs

Defect in α-keto acid dehydrogenase

Hallmark = sweet smelling urine

Seizures, eyes will not blink for minutes at a time

Treatment

- protein free diet

Front 14

Cystathioninuria

Back 14

Buildup of excess cystathionine due to defect in cystathionase

- requires PLP

- Vitamin B₆ deficiency

Common in premature infants

Autosomal recessive disease in adults

Front 15

Homocystinuria

Back 15

Inability to properly metabolize methionine

Buildup of first metabolite homocysteine leads to dimerization of homocysteine molecules via the formation of disulfide bridges

Clinical presentation is very similar to Marfans