Biochemistry Metabolism Flashcards
What processes occur in mitochondria?
Fatty acid oxidation (Beta oxidation), acetyl CoA production, TCA cycle, oxidative phosphorylation
What processes occur in cytoplasm?
glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER), cholesterol synthesis
What processes require both cytoplasm and mitochondria:
HUG: heme synthesis, urea cycle, gluconeogenesis
kinase
uses ATP to add high energy phosphate
phosphorylase
adds inorganic phosphate w/out using ATP
phosphatase
removes phosphate group
dehydrogenase
catalyzes ox-redox reactions
hydroxylase
adds -OH group onto substrate
carboxylase
transfers CO2 group with help of biotin
mutase
relocates functional group within molecule
RDS: glycolysis
PFK-1; +: AMP, F26BP; -: ATP, citrate
RDS: gluconeogenesis
F16BPhosphatase; + ATP, acetyl-CoA; - AMP F26BP
RDS: TCA cycle
isocitrate dehydrogenase; + ADP; - ATP, NADH
RDS: glycogenesis
glycogen synthase; + G6P insulin, cortisol; - epinephrine, glucagon
RDS: glycogenolysis
glycogen phosphorylase; + epinephrine, glucagon, AMP; - G6P, insulin ATP
RDS: HMP shunt
G6PD; + NADP, - NADPH
RDS: de novo pyrimidine synthesis
Carbamoyl phosphate synthetase II
RDS: do novo purine synthesis
Glutamine-PRPP amidotransferase: -AMP, IMP, GMP
RDS: urea cycle
carbamoyl phosphate synthetase I: + n acetyl glutamate
RDS: fatty acid synthesis
acetyl-coa carboxlyase: + insulin, citrate; - glucagon, palmitoyl coA
RDS: fatty acid oxidation
carnitine acyltransferase: - malonyl coA
RDS: ketogenesis
HMG-coa synthase
RDS: cholesterol synthesis
HMG coA reductase: + insulin, thyroxin, - glucagon, cholesterol
which enzymes require biotin as a cofactor?
pyruvate carboxylase (pyruvate to OAA); acetyl coA to malonyl coA; propionyl COA to methylmalonyl COA
which enzymes require thiamine?
Transketolase (ribulose 5 phosphate to F6P); pyruvate DH (pyruvate to acetyl CoA); a-ketoglutarate DH (alphaKG to succinyl coA)
where is NADPH made? used?
product of HMP shunt; used in anabolic processes, respiratory burst, CYP450 system, glutathione reductase
hexokinase vs glucokinase
hexokinase in most tissues except liver/B cells of pancreas; low Km; high affinity; low Vmax and capacity; not induced by insulin; feedback inhibited by G6P; not associated with mature onset diabetes; glucokinase is opposite of hexokinase
galactokinase
galactose to galactose 1 phosphate; mild galactosemia
galactose 1 phophate uridyltransferase
glactose 1 phosphate to glucose 1 phosphate; severe galactosemia
aldolase A vs B
aldolase A–muscle, B–liver; glyceraldehyde 3 phosphate/DHAP to fructose 1,6 bisphosphate
hexokinase/glucokinase
Glucose to glucose 6 phosphate; irreversible
Glucose 6 phosphatase
glucose 6 phosphate to glucose; irreversible; von Gierke’s
G6PD
glucose 6 phosphate to 6 phosphogluconolactone; irreversible
transketolase
ribulose 5 phosphate to fructose 6 phosphate; requires thiamine
PFK-1
fructose 6 phosphate to F16BP; irreversible
Fructose 1,6 bisphosphatase
F16BP to F6P; irreversible
fructokinase
fructose to F1P; essential fructosuria
aldolase B
F1P to DHAP/glyceradehyde, fructose intolerance
pyruvate kinase
PEP to pyruvate; irreversible
pyruvate DH
pyruvate to acetyl coA; requires thiamine; irreversible
HMG coA reductase
HMG coA to mevalonate
pyruvate carboxylase
pyruvate to OAA; irreversible, requires biotin
PEP carboxykinase
OAA to PEP; irreversible
citrate synthase
OAA to citrate;
isocitrate dehydrogenase
isocitrate to alpha ketoglutarate; irreversible
alpha KG DH
a KG to succinyl coA; irreversible, requires thiamine
ornithine transcarbamoylase
ornithine + carbamoyl phosphate to citrulline
Which reactions in glycolysis produce ATP?
phosphoglycerate kinase (13BPG to 3 PG, reversible); pyruvate kinase (PEP to pyruvate, irreversible)
fasting state regulation by F26BP
increased glucagon–>increased cAMP–>increased protein kinase A–>increased FBPase2, decreased PFK2, less glycolysis
fed state regulation by F26BP
increased insulin–>decreased cAMP–>decreased PKA–>decreased FBPase2, increased PFK2, more glycolysis, less gluconeogenesis
pyruvate dehydrogenase complex requires which cofactors:
pyrophosphate (B1, thiamine, TPP); FAD (B2, riboflavin); NAD (B3, niacin); CoA (B5, pantothenate); lipoic acid
vomiting, rice water stools, garlic breath
arsenic poisoning, inhibits lipoic acid, disrupts pyruvate DH complex
purely ketogenic AAs
lysine, leucine
neurologic deficits, lactic acidosis, increased serum alanine since infancy
pyruvate dehydronase complex deficiency; buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT); Tx with high intake of ketogenic nutrients
pyruvate can be shunted to 4 different pathways:
alanine amiotransferase (ALT) to alanine (requires B6); pyruvate carboxylase (requires biotin) to OAA (replenish TCA cycle or be used in gluconeogenesis); pyruvate DH (connect glycolysis to TCA cycle); LDH (requires B3)
Rotenone
inhibits Complex I of ETC
succinate dehydrogenase
part of TCA and Complex II of ETC
Antimycin A
inhibits Complex III of ETC
Cyanide, CO
inhibits complex IV of ETC
oligomycin
inhibits complex V of ETC (ATP synthase)
contains CoQ and cytochrome C
Complex III of ETC
reduces oxygen to water in ETC
complex IV
which side of mt membrane is proton gradient formed on?
proton gradient is formed in intermembrane space and flows through complex V on inner mt membrane to the mitochondrial matrix
2,4 dinitrophenyl
increase permability of membrane; uncouple ETC, produces heat
what are uncoupling agents?
2,4 dinitrophenyl, aspirin (fevers after OD), thermogenin in brown fat
what reaction in gluconeogenesis requires GTP?
PEP carboxykinase (OAA to PEP)
odd chain vs even chain fatty acids in gluconeogenesis
only odd chain fatty acids can participate; converted to proprionyl CoA and enter TCA as succinyl cOA; even chain FAs yield only acetyl CoA
patients with CGD are at risk for what types of infection?
catalase + bugs: aspergillus, S aureus
pyocyanin
released by pseudomonas aeruginosa to generate ROS to kill competing bacteria
lactoferrin
protein found in secretory fluid and neutrophils that inhibits bacterial growth via iron chelation
failure to track objects or develop a social smile
galactokinase deficiency; galactitol accumulates in lens–infantile cataracts
failure to thrive,jaundice, hepatomegaly, infantile cataracts, retardation
classic galactosemia, uridyltransferase deficiency; tx by excluding galactose and lactose
Schwann cells, retina, and kidneys lack what enzyme that makes them prone to damage by hyperglycemia
they have aldose reductase but lack sorbitol dehydrogenase, which results in accumulation of sorbitol->osmotic damage
glucogenic essential amino acids:
methionine, valine, histidine
glucogenic/ketogenic essential amino acids
isoleucine, phenylalanine, threonine, tryptophan
Ketogenic essential amino acids
lysine, leucine
which step of urea cycle requires N-acetyl glutamate as cofactor?
carbamoyl phosphate synthetase I (CO2 + NH3 to carbamoyl phosphate) requires 2 ATP; occurs in mitchondria
which step of urea cycle generates AMP?
argininosuccinate synthetase: citrulline + aspartate to argininosuccinate requires ATP and generates AMP
which step of urea cycle generates fumarate?
argininosuccinase: argininosuccinate to arginine generates fumarate
which step of urea cycle generates urea?
arginase: arginine + H2O to ornithine and urea (to kidney)
urea is comprised of what three things?
ammonia; carbon dioxide; aspartate; NH2-C=O-NH2
ammonia is transported from muscle to liver how?
amino acids to glutamate to alanine–>bloodstream–>liver–>glutamate–>urea; pyruvate + NH3 = alanine; alpha KG + NH3 = glutamate
urea cycle occurs mostly in?
liver; impaired in liver disease
N-acetyl glutamate deficiency vs carbamoyl phosphate synthetase deficiency
NAG deficiency is AR, CPS is X linked recessive; both present identically: early in life, orotic acid elevated in blood and urine; decreased urea production; hyperammonemia; no megaloblastic anemia; increased ornithine with normal urea cycle enzymes suggests NAG deficiency
carbamoyl phosphate synthetase deficiency vs orotic aciduria
orotic aciduria: UMP synthase (orotic acid to UMP) deficiency (de novo pyrimidine synthesis); no hyperammonemia; megaloblastic anemia
Catecholamine synthesis pathway:
Phe–>Tyrosine–>Dopa–>Dopamine–>NE–>Epi-; cofactors required in order: BH4, BH4, B6, vitC, SAM; Enzymes: phenylalanine hydroxylase, tyrosine hydroxylase, dopa decarboxylase, dopamine hydroxlyase,
Tyrosine can form what three products:
Dopa or Thyroxine, homogentisic acid
DOPA can form what two products:
Melanin or Dopamine
tryptophan forms which AAs
niacin (requires B6) to NAD/NADP+, serotonin (requires BH4 and B6); serotonin to melatonin
histidine forms which AAs
histamine (requires B6)
Glycine forms which amino acids
porphyrin (requires B6)–>Heme
Glutamate forms which amino acids
GABA (requires B6); glutathione
Arginine forms which AAs
creatine, urea, Nitric oxide (requires BH4)
Phenlyketonuria can be caused by:
deficiency in phenylalanine hydroxylate or BH4 (malignant PKU); Tx by reducing Phe intake and increased tyrosine intake
maternal PKU
infant microcephaly, intellectual deficiency, growth retardation, congenital heart defect
alkaptonuria
AR deficiency of homogentisate oxidate in degradative pathway of tyrosine to fumarate
dark connective tissue, brown sclerae, urine turns black on prolonged air, may have debilitating arthralgias
alkaptonuria–homogentisate oxidate deficiency; AR; homogentisate acid buildup in cartilage
albinism
tyrosinase deficiency–cannot convert DOPA to melanin
inhibits DOPA decarboxylase
carbidopa
3 deficiencies resulting in homocystinuria
cystathione synthase deficiency (Tx by decreasing methionine, increasing cysteine, increase B12 and folate in diet); decreased affinity of cystathione synthase for pyridoxal phosphate (increase B6 and cysteine in diet); Homocystein methyltransferase deficiency (increase methionine in diet)
homocystinuria vs marfans?
marfans has negative nitroprusside test. lens up and out in marfans; homocystinuira lens down and in;
cystinuria
defect of renal PCT COLA transporter (cysteine, ornithine, lysine, arginine); excess cystine in urine–>hexagonal uric acid stones; AR; nitroprusside test positive; Tx with urinary alkalinization (potassium citrate, acetazolamide) and chelating agents, hydration
urine smells like burnt sugar
MSUD: blocked degradation of ILV (isoleucine, leucine, valine) due to decreased alpha-ketoacid dehydrogenase (B1); Tx AA restriction with B1 supplementation;
Glycogen phosphorylase vs glycogen synthase
phosphorylase (glycogen to glucose) is activated by glycogen phosphorylase kinase (via glucagon, epinephine and PKA and calcium); synthase (glucose to glycogen) is activated by insulin; PKA inhibits synthase; protein phosphatase inhibits phosphorylase
severe fasting hypoglycemia, increased glycogen in liver, high blood lactate, hepatomegaly
Type I glycogen storage disease (von Gierke); glucose 6 phosphatase defect–>cant release glucose from liver into bloodstream; tx with frequent carbs, avoid fructose and galactose (both are converted to glucose 6 P)
cardiomyopathy and systemic findings–>early death
Type 2 GSD (Pompe disease); lysosomal alpha 1,4 glucosidase (acid maltase) deficiency;
milder hypoglycemia, normal blood lactate levels
Type 3 (Cori disease); debranching enzyme (alpha 1,6 glucosidase); intact gluconeogenesis just can’t utilize all of glycogen
increased glycogen in muscle, painful muscle cramps, myoglobinuria (red urine) with strenous exercise, arhythmia from electrolyte disturbances
Type V (McArdle disease); skeletal muscle glycogen phosphorylase (myophosphorylase); can’t break down glycogen in muscle
all glycogen storage disease are inherited in what fashion?
AR
peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
Fabry disease; alpha galactosidase A, accumulation of ceramide trihexoside; XR
HSM, pancytopenia, aseptic necrosis of femur/bone crises, lipid laden macrophages,
Gaucher disease, glucocerebrosidase (beta glucosidas), accumulation of glucocerebroside, AR
progressive neurodegeneration, HSM, cherry red spot on macula, foam cells (lipid laden macrophages)
Niemann Pick disease; sphingomyelinase; accumuation of sphingomyelin, AR
progressive neurodegeneration, developmental delay, cherry red spot on macula, lysosome with onion skin, no HSM
Tay Sachs, hexosaminidase A, GM2 ganglioside accumulation, AR
Peripheral neuropathy, developmental delay, optic atrophy, globoid (multinucleated) cells
Krabbe disease, Beta galactosidase (galactocerebrosidase); galactocerebroside/psychosine; AR
central and peripheral demyelination with ataxia, dementia
metachromatic leukodystrophy; arylsulfatase A; cerebroside sulfate, AR
developmental delay, gargolyism, airway obstruction, corneal clouding, HSM
Hurler syndrome; alpha L iduronidase; heparan sulfate, dermatan sulfate, AR
Mild hurler + aggressive behavior, no corneal clouding
Hunter Syndrome; iduronate sulfatase; heparan sulfate/dermatan sulfate; XR
Which sphingolipidoses LSD is XR?
Fabry’s all others are AR
Which mucopolysaccharidoses is XR?
hunter’s; hurlers is AR
weakness, hypotonia, hypoketotic hypoglycemia
carnitine deficiency (cannot transport LCFAs into mitochondria, toxic accumulation of FAs)
acyl-coA deficiency
increased dicarboxylic acids, decreased glucose and ketones, acetyl coA is + allosteric regulator of pyruvate carboxylase in gluconeogenesis; decreased acetyl CoA, decreased fasting glucose
ketone bodies
acetoacetate and B-hydroxybutyrate; urine test does not detect B hydroxybutyrate
ketone bodies cannot be utilized as fuel where?
liver (no thiotransferase); RBCs (no mitochondria); renal medulla (not enough oxidative capacity)
pancreatic lipase
degradation of dietary TGs in small intestine
lipoprotein lipase
degradation of TGs circulating in chylomicrons and VLDLs, found on vascular endothelial cell surface; activated by insulin
hepatic TG lipase
degradation of TG remaining in IDL
hormone sensitive lipase
degradation of TGs stored in adipocytes
LCAT
esterifies cholesterol (nascent HDL to mature HDL)
CETP
transfer of cholesterol esters from HDL to VLDL/IDL/LDL
chylomicrons vs VLDL
chylomicrons carry TGs from food to peripheral tissues. VLDL carries endogenous TGs from the liver; chylomicrons: ApoB48, VLDL ApoB100
lipoprotein lipase cofactor
ApoCII
mediates remnant uptake
ApoE
activates LCAT
Apo A-I
mediates chylomicron secretion
B-48
binds LDL receptor
B-100
