Protein And Amino Acid Metabolism Flashcards
What happens to excess amino acids in the body
Cannot be stored so used for fuel
Kwashiorkor
Protein deficiency but adequate calories
Famine edema
Inadequate synthesis of plasma proteins like albumin so fluid Escape into tissues (oncotic pressure)
Marasmus
Protein calorie deficiency
Starvation
People at risk of protein malnutrition
Pregnant and lactating women
individuals with eating disorders
chronic alcoholics
substance abusers
hospital patients with major protein
needs
elderly
clinical chronically ill
individuals patience with genetic disorders in amino acid metabolism
Essential amino acids (PVT TIM HALL)
Phenylalanine
Valine
Tryptophan
Threonine
Isoleucine
Methionine
Histidine
Arginine
Leucine
Lysine
Is arginine always an essential amino acids
No
essential in children because of active growth but nonessential in adults
What is a glucogenic Amino acid
Product can enter gluconeogenesis
What is a ketogenic amino acid
Product intermediate of lipids metabolism or Ketone bodies
Positive nitrogen balance
More intake than excretion
Growth, pregnancy, tissue repair
Negative N balance
N excretion > intake
Starvation
Malnutrition
Illness
Surgery
General rédaction of amino acids
Transamination
Oxidative deamination
Decarboxylation
Transdeamination
Transamination
Caralyzed by transaminases (aminotransferase)
Transfer of NH2 to produce another AA
Co factor of transaminases
Pyridoxal phosphate from vit B6
Main compound in AA metabolism
Glutamate
Glutamine
a-KG
Neutral transport and storage form of ammonia
Glutamine
Glutamate dehydrogenase rxn
a-KG ——-> glutamate by glutamate dehydrogenase
Glutamate ——> glutamine by glutamine synthétase
Glutamine —-> glutamate by glutaminase
Genetic disorder in which glutamate dehydrogenase always activated due to binding site of GTP mutation
Hyperinsulinism - hyperammonemia syndrome with hypoglycemia
Where in the body do you find amino acids oxidase
The kidney
Decarboxylation of AA
Removal of CO2 by glu decarboxylase to form GABA
Transdeamination
Coupling of aminotransferase
with glutamate dehydrogenase reaction ( transamination+ deamination )
Tryptophan metabolized to
97%: Alanine Acetyl Coa CO2 Formate
3% :
Melatonin
Serotonin
Nicotinate ( niacin )
Serotonin function
Neurotransmission Behavioral processes (!appetite, agression , sleep ,sensory perceptions, depression Vasoconstriction Regulate circadian cycle , intestinal peristalsis
Agonist of serotonin
LSD
Antidepressants and their MOA
Paxil
Prozac
Zoloft
Inhibits serotonin reuptake
Hartnup disease
Defect in transportation or absorption of amino acids in intestine
Leads to essential amino acid deficiency and nicotinamide deficiencies
Hartnup disease symptoms
Hereditary pellagra like skin rash
Temporary cerebellum ataxia
Renal amino aciduria
Hartnup disease 3 D’s
Dermatitis
Diarrhea
Dementia
What factors precipitate hartnup disease
Sunburn Fever Inadequate nutrition Irregular diet Stress
Under what form is NH3 excreted
Urea
Direct sources of ammonia in liver
Glutamate
Glutamine (extrahepwtic tissues )
Alanine (muscles )
Organs that contributes the most to waste nitrogen
Muscles
Allostérie activator of CPSI
N acetylglutamate
Difference between CPSI and CPSII
CPSI only in mitochondria and uses NH3 in urea cycle
CPSII only in cytosol and uses glutamine in pyrimidine synthesis
Organ where urea cycle takes place
Liver
Reactions of urea cycle in mitochondria
Ammonia —-> carbamoyl phosphate
By CPSI
Carbamoyl phosphate —-> citrulline
By ornithine transcarbamoylase and addition of ornithine
Urea cycle rxn in cytosol
Citrulline —-> argininosuccinage
By argininosuccinate synthase and addition of aspartic acid
Argininosuccinate —-> arginine
By argininosuccinase and removal of fumarate
Arginine ——> ornithine
By arginase and removal of urea
Fate of fumarate in urea cycle
Glucose source
Aspartate source
Energy source
2 hypothesis of urea malfunctions leading to coma
Depletion of a-KG because too much NH4 allow conversion of a-KG to glutamate by glutamate dehydrogenase. So less a-KG free for TCA cycle -> less oxidative phosphorylation which is important for neurons
Toxicity of glutamine due to its accumulation in astrocytes. Leads to osmotic pressure -> swelling -> edema
Clinical manifestations of urea cycle malfunctions
Vomiting Seizures Somnolence Coma Death
Most common urea cycle enzyme malfunction
Ornithine gras carbamoylase
Symptoms of hyperammonemia type 2 (ornithine transcarbamoylase deficiency)
Mild : episodic hyperammonemia when high protein intake or infection
Severe : neonatal hyperammonemic coma, death , mental retardation, cerebral palsy when survive
High glutamine level
Hyperammonemia type 1 due to
CPSI deficiency
Citrullenemia
Hyperammonemia + high citrulline level
Due to argininosuccinate synthase deficiency
Management of citrullinemia
Arginine feeding (enhance citrulline excretion )
Benzoate feeding (divert ammonia to hyppurate)
Emergency Management of hyperammonemia
IV glucose and lipid (stop protein catabolism )
Hemodialysis
Phenylacetate for gln conjugation-> enhance n acetylglutamate synthase
Long term Management of hyperammonemia
Less dietary protein intake Adequate essential AA Non protein calories Arginine or citrulline if necessary Drugs (phenylbutyrate , benzoate)
Phenylalanine main product
Tyrosine
Tyrosine metabolism end product
Fumarate + acetoacetate
Phenylalanine metabolism overview
Phe ——> tyrosine
By phe hydroxylase + H4biopterin
Tyr——> p hydroxylphenyl pyruvate
By aminotransferase
hydroxylphenyl pyruvate —-> homogentisate
By oxidase
Homogentisate —-> maleyl acetoacetate
By oxidase
Maleyl acetoacetate ——> fumaryl acetoacetate
By isomerase
Fumaryl acetoacetate——> acetoacetate + fumarate
By hydrolase
Tyrosinemias
Deficiency in tyr aminotransferase
Accumulation of tyr and metabolites
Type II Tyrosinemias (oculocutaneous)
Eye & skin lesions
Mental retardation
Cornea keratitis
Palm hyperkeratosis +ulcers
Type I tyrosenemias (hepatorenal )
Liver failure
Renal tubular dysfunction
Rickets
Polyneuropathy
Caused by fumarylacetoacetate hydrolase deficiency
Type I tyrosinemia management
Diet
Nitisone
Liver transplant
Alcaptonuria
homogentisate oxidase deficiency so accumulation of homogentisate in urine
Urine looks intense dark color
Deposition of dark pigment in cartilage and connective tissue
Albinism
Deficiency of tyrosinase
So no skin or hair color
Sun sensitivity
Photophobia
Phenylketonuria
Phenylalanine hydroxylase deficiency (classical) Or H4biopterin deficiency (non classical)
Phenylketonuria symptoms
Mental retardation
Seizures
Microcéphaly
PKU type I management
Low diet in phe
Adequate diet with tyrosine
Screening of neonate so that therapy can work
Long term maintenance of diet
Tyrosine precursors of
Catecholamines ( l dopa, dopamine , norepinephrine , epinephrine
Treatment of Parkinson’s disease
Dopa because can cross blood brain barrier ( dopamine can’t )
If high level of homovanillate , what does it mean
Dopamine metabolism malfunction
If high level of vanillykmandelate, what does it mean
Epinephrine and norepinephrine metabolism malfunction
Branched chain AA
Leucine
Isoleucine
Valine
Leucine catabolism
Leucine ——> isovaleryl coa ——> acetoacetyl coa
Valine and isoleucine catabolism
Aa —-> some buturyl stuff ——-€ propionyl COA —biotin—-> methylmalonyl coa ——> succinyl coa
Disorders of BCAA
Propionicacidemia
Maple syrup disease
Isovaleric acidemia
Methylmalonicacidemi
Propionic acidemia
Deficient carboxylase or biotin preventing formation of methylmalonyl coa
So propionyl coa accumulation
Propionicacidemia symptoms
Hypoglycemia
Hyperammonemia
Less succinyl coa
Maple syrup urine disease
Val île leu metabolism blocked because ketoacid dehydrogenase deficient
So hypoglycemia and ketoacidosis
Mental retardation
Isovaleric acidemia
Isovaleryl coa dehydrogenase deficiency
Isovaleryl coa accumulation So form toxic metabolites in kidney (isovaleryl glycine, isovalerylcarnitine )
Isovaleric acidemia symptoms
Coma
Acidosis
Ketonuria
Sweaty feet odour
Isovaleric acidemia management
Diet management
Newborn screening
Crisis management
Methylmalonic acidemia
Defective methylmalonyl mutass or cobalamin
So methylmalonyl coa accumulation which inhibits pyruvate carboxylase
Methylmalonyl acidemia symptoms
Hyperammonemia Coma Nephropathy CNS involvement Hypoglycemia Ketoqcidosis
Cysteine synthesis pathway
Homocysteine + serine ——> cystathione
By cysthationine synthase
cystathionine——> a-ketobutyrate and cysteine
By cystathionase
Cofactor needed for cysteine synthesis
PLP (pyridoxal phosphate )
Homocysteine synthesis pathway
Methionine ——> s Adenosylmethionine
s Adenosylmethionine —-> a adenosylhomocysteine
S adenosylhomocysteine—-> homocysteine
How to get from homocysteine to methionine
Add vit b12 + folic acid
Hypercysteinemja
Deficiency of cystathionine synthase
Accumulation of homocysteine
And remethylation causes high methionine levels
Hyperhomocysteinemoa symptoms
Mental retardation
Dislocated lenses after age 3
Osteoporosis
Management of hyperhoomocysteinemia
Restrictions of methionine intake
Feeding of beta une and pyridoxine
Feeding of folate
What disease is high level homocysteine associated with
Mortality in coronary heart disease
Dementia
Alzeihmer disease
Methyl donor to homocysteine to obtain methionine
N5-methyltetrahydrofolate
Serine precursor
Glucose
Glycine precursors
Serine or threonine
