AA Metabolism (Biochem) Flashcards
1
Q
Main classes of antifungal medications
A
polenes: ampho and nystatin
triazoles: azoles
echinocandins: fungins
pyrimidines: flucytosines
2
Q
How does the body get rid of excess N
A
- through urine - excess N converted to urea in the liver and goes through kidney –> eliminated in urine - the kidney adds small quantities of ammonium ion to the urine in part to regulate acid-base balance, but also to eliminate N - amino groups released by deamination runs form ammonium ion (NH4+) which must not escape into peripheral blood hyperammonemia: toxic effects on the brain (cerebral edema, convulsions, coma, death) - most tissues add excess N to the blood as glutamine by attaching ammonia to the gamma-carboxyl group of glutamate - Muscle sends N to the liver as alanine and smaller # of other aa including glutamine
3
Q
Glutamine Synthetase
A
- in most tissues - captures excess N by laminating glutamate to form glutamine - IRREVERSIBLE Rxn - Glutamine (relatively nontoxic): the major carrier of excess N from tissues
4
Q
Glutaminase and the Kidney
A
- in the kidney, intestine, and small amounts in the liver - deaminates glutamine (arriving from the blood) - eliminates amino group as ammonium ion (NH4+) in the urine - IRREVERSIBLE Ron - KIDNEY glutaminase induced by chronic acidosis: excretion of ammonium may become the major defense mechanism) High levels of Glutaminase in the intestine (where ammonium ion from deamination can be sent directly to the liver via the portal blood and used for urea synthesis) -intestinal bacteria and glutamine from dietary protein contribute to the intestinal ammonia entering the portal blood
5
Q
Aminotransferases (aka transaminases)
A
- in both liver and muscle - do not release the amino groups as free ammonium - transfer the amino group from 1 AA to another (usually alpha-ketoglutarate, a CAC intermediate) - Pyridoxal phosphate (PLP) derived from Vitamin B6 is required to mediate the transfer - named by the AA donating the amino group to alpha-ketoglutarate. - Ex) alanine aminotransferase (ALT) - Ex) aspartate aminotransferase (AST) - in pathologic conditions may leak into blood = indicate liver or muscle damage
6
Q
Glutamate Dehydrogenase
A
- found in many tissues - REVERSIBLY deaminates Glutamate - produces alpha-ketoglutarate (CAC intermediate)
7
Q
What is the major carrier of excess N from tissues
A
- Glutamine (relatively nontoxic) - most tissues add excess N to the blood as glutamine by attaching ammonia to the gamma-carboxyl group of glutamate - Muscle sends N to the liver as alanine and smaller # of other aa including glutamine
8
Q
What are the sources of N for the urea cycle?
A
NH3 and aspartate
9
Q
Urea cycle
A
- urea contains 2 N and is synthesized in the liver from aspartate and carbamoyl P - carbamoyl P: made from ammonium ion (NH4+) and CO by mito carbamoyl phosphate synthase (requires N-acetylglutamate as an activator) - N-acetylglutamate is only produced when free AA are present - rate-limiting enzyme: mito carbamoyl phosphate synthase - acts catalytically - small # of the intermediates can synthesize large # of urea - occurs partially in the mito and partially in the cytoplasm - citrulline enters cytoplasm and ornithine returns to the mitochondria (mitochondrial ornithine transcarbamoylase)
10
Q
if gluconeogenesis is active, fumarate can be converted to
A
glucose
11
Q
the product of the urea cycle (urea) is formed in the
A
cytoplasm and enters the blood of delivery to the kidney
12
Q
Carbamoyl Phosphate Synthetase Deficiency * remember, this is a mitochondrial enzyme
A
- increased [NH4+]; hyperammonemia
- increased blood glutamine
- decreased BUN
- No orotic aciduria* (no excretion of orotic acid in urine) -
AR*
- cerebral edema (lethargy, convulsions, coma, death)
13
Q
Ornithine Transcarbamoylase Deficiency * remember, this is a mitochondrial enzyme
A
- increased [NH4+]; hyperammonemia
- increased blood glutamine
- decreased BUN
- orotic aciduria** (excretion of orotic acid in urine)
- X-Linked Recessive**
- cerebral edema (lethargy, convulsions, coma, death) *
- Without OTC, Carbamoyl P accumulates in mito and leaks into the cytoplasm
- Carmaboyl P is first substrate in pathway of orotic acid metabolism
14
Q
Phenylalanine Hydroxylase Deficiency (Phenylketonuria aka PKU)
- birth appearance
- sx
- urine smell
- appearance of child
- dietary modifications needed
- labs
A
- 1:15,000 - normal at birth. If untreated: slow development, - severe mental retardation, autistic symptoms - loss of motor control - musty odor to urine bc there’s an increase in phenyl-ketones - kids have pale skin and white-blonde hair - sx from high levels pf he and not to the phenylketones. Tx: diet LOW in phe (but still need some bc essential AA) - avoid aspartame - diet important during pregnancy: infants born to PKU mothers have microcephaly, mental retardation and low birth weight - screen infants a couple days after birth
15
Q
MCC elevated BUN
A
dehydration
16
Q
Transaminases use what as a coenzyme?
A
- Vitamin B6 aka pyridoxine
17
Q
Seeing alanine in the blood is a sign of
A
starvation
18
Q
IF BUN is too high
A
kidney dysfunction
19
Q
if BUN is too low
A
liver dysfunction
20
Q
What causes Parkinson’s Diasease?
A
- loss of dopamine producing cells in the brain - catecholamines (Dopamine) don’t enter the brain, brain synthesizes them locally - L-dopa can cross the BBB - Sx: bradykinesia - mask-like facies - pill rolling, RESTING tremor - cogwheel rigidity
21
Q
Homogentisate Oxidate Deficiency
A
causes: alcaptonuria
- Homogentistic acid accumulates in the blood - excreted in urine–>
- darkens when exposed to air
- Dark pigment: accumulates over years in cartilage: ochronosis
- seen in the sclera of the eye and in ear cartilage
- puts develop arthritis in adulthood
- usually in 3rd decade
- Sx not present in all patients w enzyme deficiency
22
Q
Branched Chain Ketoacid Dehydrogenase Deficiency
A
Maple Syrup Urine Disease
BCKDH: metabolizes branched-chain ketoacids (derived from valine, leucine and isoleucine)
- infants normal for the first few days of life–>
- progressive lethargy
- weight loss
- alternating episodes of hypertonia and hypotonia
- urine develops a maple syrup odor
- ketosis
- coma and death if not treated
- tx: restrict dietary valine, leucine and isoleucine
- Branched Chain Ketoacid Dehydrogenase similar to alpha-ketoglutarate dehydrogenase (both are TLCFN enzymes)
“Tender Loving Care For Nancy” Requires: T: Thiamine L: lipoic acid C: CoA F: FAD N: NAD+
23
Q
Propionyl-CoA Carboxylase Deficiency
A
- accumulation of propionic acid, methyl citrate, hydroxypropionic acid -
- odd-chain FA synthensis (made from valine, methionine, isoleucine and threonine through propionic acid pathway) impaired: neonatal ketosis from failure to metabolize ketoacids produced from these 4 AA
- pneonatal ketosis from failure to metabolize ketoacids produced from these 4 AA
24
Q
When a biochemical reaction requires a methyl group (methylation) what is the usual methyl donor?
A
S-adenosylmethionine (SAM)
25
Q
Alcaptonuria
A
- Homogentisate Oxidate Deficiency - accumulation of homogentistic acid in the blood - causes excretion in urine, which darkens when exposed to air - Dark pigment also accumulates over years in cartilage (ochronosis) - and may be seen in the sclera of the eye, in ear cartilage - puts develop arthritis in adulthood, usually in 3rd decade - Sx not present in all patients w enzyme deficiency
26
Q
Maple Syrup Urine Disease
A
- Branched Chain Ketoacid Dehydrogenase Deficiency - BCKDH metabolizes branched-chain ketoacids produced from their cognate AA: valine, leucine and isoleucine) - infants normal for the first few days of life - progressive lethargy, weight loss - alternating episodes of hypertonia and hypotonia - urine develops a maple syrup odor - ketosis, coma and death if not treated - tx: restrict dietary valine, leucine and isoleucine - Branched Chain Ketoacid Dehydrogenase is similar to alpha-ketoglutarate dehydrogenase (both are TLCFN enzymes) “Tender Loving Care For Nancy” Requires: T: Thiamine L: lipoic acid C: CoA F: FAD N: NAD+
