Amino Acid Metabolism Flashcards
What are the Essential AAs?
PVT TIM HALL
How are amino group amino acids removed?
Urea Cycle
Keteogenic AAs are broken down to…
Acetyl CoA or Acetoacyl CoA
Glycogenin AAs are broken down to…
- Pyruvate
- 3-PG
- OAA
- a-KG
- Succinyl CoA
- Fumarate
What is Pyridoxal phosphate?
Vitamin B derivative acts as CoEnzyme for transamination reactions
What is the clinical significance of AST/ALT?
- Both are enzymes in transamination rxns
- Released into blood in Hepatic disease
- Diagnostic marker
Which organ mainly operates urea cycle?
Liver
How does NH3 affect pH?
Takes up H+ —> Alkalosis
What happens to glutamine After it reaches liver?
- Converted to glutamate and ammonia
- Ammonia enter urea cycle
What are the possible fates of glutamate?
- Urea
- Polyamine
- Glutathione
- GABA
- aKG (Glutamate DH)
- Glutamine (Glutamine Synthetase)
Describe the synthesis of Carbachol Phosphate.
NH4+ + HCO3- —> Carbomoylphosphate
- Uses 2 ATP
- CSP-I enzyme
- CSPI is in Mt and is allosteric regulated by N-Acetyl glutamate
What is normal BUN?
BUN (Blood Urea Nitrogen) is 10-20 mg/dL normally
What is the Cory Cycle, and it’s significance?
- Glucose-Alanine cycle btwn Muscle and Liver
- Muscle produces Alanine —> Liver
- Liver Uses Alanine and a-KG to produce Pyruvate and glutamate
- Pyruvate made into glucose in liver
What are the main functions of serotonin?
- Regulation of Temp and BP
- Vasoconstrictor and smooth muscle contraction
What is a Phechromocytoma?
Tumors of chromaffin tissues:
overproduction of catecholamines,
resulting in hypertension.
What is the pathology of Albinism?
- Tyrosinase deficiency leading to melanin deficiency
- Skin susceptible to sun damage
What are normal Blood creative levels?
<1.5 mg/dL
What is the role of Glutathione?
- Maintains protein thiol groups in their reduced state.
* In liver detoxifies xenobiotics (drugs, food additives etc).
What are products and reactants in NO Synthesis?
Arginine + O2 + NADPH —> NO + Citrulline
- NO Synthase
- THB -> DHB
What are clinical correlations associated with AA metabolism in neurotransmission?
- Microglia in Brain immune system
- MS
- Epilepsy
- Plant and snake Poison
- Organophosphonates
What are Ach inhibitors?
Physostigmine and Neostigmine
What is a clinical correlation for disruption of production of Proline?
Scurvy
- Hydroxyproline —> Hydroxylases require Vitamin C
Clinical consideration: Phenylalanine metabolism
- Phenylketonuria: Mousy odor, light pigmentation, peculiarities of gait, eczema, dev delay
Clinical consideration: Tyrosine degradation
- Accumulation of Homogentisate
- Dark brown polymer in joints —> Arthritis
What is produced in methionine metabolism? Significance?
SAM - Methylates various compounds in chemical processes like Creatine synthesis, catecholamines synthesis, etc
Clinical correlation: Cysteine Synthesis
- Defects in Cystathione synthase result in accumulation of homocysteine and methionine in blood and urine
- Skeletal deformations, thrombosis, mental retardation
Clinical correlation: Sulfur amino acids
Cystinuria: Defects in membrane transport of dietary cysteine through epithelial cell
- Forms kidney stones
Clinical correlation: Homocysteine
Intermediate which Thioesterase LDL—> Atheromas
Clinical correlation: Methionine and Branched chain AAs
Maple Syrup Urine Disease: Deficiency in Branched chain keto acid DH
- High in Mennonite Population
Clinical Correlation: Methylmalonic acidemia
- Methylmalonyl AoA mutate Missing
- Conversion of B12 sometimes missing
- Metabolic Acidosis and mental retardation
Clinical correlation: Histidine metabolism
Histidinemia:
- Deficiency Of Histidase
- Mainly affects skin and Liver
- Confirmed through skin biopsy
Which AA is used to create Carnitine?
Lysine
Clinical Significance: THF
- Folic Acid (B9)
- THF is synthesized in certain microorganisms
- Essential nutrient to humans
- Inhibited by Sulfonamides
Glutamine —> Glutamate
Glutaminase
What is Vitamin B6, and what reactions is it needed for?
Pyridoxal Phosphate:
Decarboxylases:
- Histamine Production
- GABA production
- Dopamine production
- Cysteine Production: Homocysteine —> Crystathione —> Cysteine (BOTH STEPS)
What is Homocystinuria? Differentiate classical and non classical.
Build up of Homocysteine
Classical (Enzyme):
- Crystathione B-Synthase
- Methionine Synthase (Methionine Resynthesis)
NonClassical:
- Vitamin B6 (Pyridoxal Phosphate)
- Vitamin B12 (Methionine Resynthesis)
- THF Deficiency (Folate Trap)
What is Crystathionuria? Differentiate Classical and non classical.
Build up of Crystathione
Classical:
- g-Crystathionase
NonClassical:
- Vitamin B6 (Pyridoxal Phosphate)
What AA metabolic processes use SAM?
- CAtecholamine synthesis
- Melatonin Synthesis
- Creatine Synthesis
- Carnitine synthesis
- Cysteine synthesis
What is Alcaptonura? What AA is involved?
Defect in Homogentisate Oxidase —> Build up of Homogentisate
Tyrosine
What is the AA involved in Pellagra? What are important products?
- Tryptophan
- Produces Niacin —> NMP + ATP —> NAD+
- Produces Glutarate
What is produced in Histidine metabolism?
- N5-Formamino THF
- Glutamate
What enzyme is defective in Histidinemia?
Histidase
What two enzymes are produces from metabolism of 3-PG?
- Serine
- Glycine
Which B Vitamin is Folic acid? What product is used to synthesize it? What chemical inhibits production?
PABA —> Folic Acid (B9)
Sulfamethoxazole inhibits
What is trimethoprim?
- Inhibits DHF —> THF
What Are causes of megaloblastic anemia? How is the pathway connected?
- Methionine Synthase deficiency
- Vitamin B12 Deficiency (Cobalamine)
- Folate Deficiency (Folate trap!)
N5-N10-MEthylene THF in Folate trap Converst dUMP —> dUTP.
Dysfunction of Conversion can result in DNA trouble!
