Biochem-Metabolism Flashcards
Mitochondria as metabolism site:
Fatty acid oxidation (B-oxidation), acteyl-coA production, TCA cycle, ketogenesis, oxidative phosphorylation (FAT KOP thought he was MITO)
Cytoplasm as metabolism site:
HMP shunt, glycolysis, steroid synthesis, protein synthesis, cholesterol synthesis
Both cytoplasm and mitochondria for metabolism?
Heme synthesis, Urea cycle, Gluconeogenesis (HUGs take two (i.e. both))
Process: Glycolysis
Rate limiting enzyme?
Regulators + and -
Phosphofructokinase-1 (PFK-1)
+AMP, fructose 2,6-biphosphate
-ATP, citrate
Process: Gluconeogenesis
Rate limiting enzyme?
Regulators + and -
Frustose-1,6,-bisphosphatase
+ ATP, acetyl-coA
-AMP, fructose 2,6-bisphosphate
Process: TCA cycle
Rate limiting enzyme
Regulators + and -
Isocitrate dehydrogenase
+ ADP
- ATP, NADH
Process: Glycogenesis
Rate limiting enzyme?
+ and - regulators
Glycogen synthase
+ Glucose-6-phosphate, insulin, cortisol
- Epinephrine, glucagon
Process: Glycogenolysis
Rate limiting enzyme?
+ and - regulators
Glycogen phosphorylase
+ Epinephrine, glucagon, AMP
-Glucose-6-phosphate, insulin, ATP
HMP shunt
Rate limiting enzyme
+ and - regulators
Glucose-6-phosphate dehydrogenase (G6PD)
+ NADP+
- NADPH
De novo pyrimidine synthesis
Rate limiting enzyme
+ and - regulator
CPS II
+ATP
-UTP
De novo purine synthesis
Rate limiting enzyme
+ and - regulator
Glutamine-PRPP-amidotransferase
-AMP, IMP, GMP
Urea cycle
Rate limiting enzyme
+ and - regulator
Carbomoyl phosphate synthetase I
+ N-acetylglutamate
Fatty acid synthesis
Rate limiting enzyme
+ and - regulator
Acetyl-CoA carboxylase
+ insulin, citrate
- glucagon, palmitoyl-CoA
Fatty acid oxidation
Rate limiting enzyme
+ and - regulator
Carnitine acyltrnasferase I
- malonyl-coA
Ketogenesis
Rate limiting enzyme
+ and - regulator
HMG-CoA synthase
Cholesterol synthesis
Rate limiting enzyme
+ and - regulator
+ Insulin, thyroxine
- glucagon, cholesterol
What monosaccharide is metabolized the fastest and why?
Fructose because it enters glycolysis after PFK-1 (a potent regulator of glycolysis)
What toxin causes glycolysis to produce zero net ATP?
Arsenic
Aerobic metabolism in heart/liver ATP production
32 ATP via malate/aspartate shuttle
Anaerobic metabolism in muscle ATP production
30 ATP via glycerol 3 phosphate shuttel
Universal electron acceptors?
NAD+, NADP+, FAD+
NAD+ is generally used in _____
Catabolic processes carry reducing equivalents away as NADH
NADPH generally used in?
What is it a producut of?
- Anabolic processes, respiratory burst, cyp450, glutathione reductase
- HMP shunt
Negative feedback on glucokinase production?
Fructose-6-phosphate
Negative feedback on hexokinase production?
Glucose-6-phosphate
Garlic breath, vomiting, rice-water stools
Arsenic poisoning
PDH complex and alphaketoglutarate dehydrogenase complex require what 5 same cofactors?
pyrophosphate (B1, thimaine;Tpp), Lipoic acid, CoA (B5, pantothenic acid), NAD (B3, niacin), FAD (B2, riboflavin)–>Tender Loving Care For Nobody
PDH complex is activated by exercise and how is it acvitvated?
Increase NAD+/NADH, Increase Calcium, Increase ADP
High Fructose 2,6 BP has what affect on alanine?
Prevents conversion of pyruvate to alanine in muscle and transport over to liver where it is converted back to pyruvate for use in gluconeogenesis (i.e. gluconeogenic conversion of alanine to glucose)
Only purely ketogenic amino acids
Lysine and leucine
Treatment of PDH complex deficiency and why?
Increase intake of ketogenic nutrients because they do not lead to formation of increase lactic acid and subsequently do not increase blood lactate levels
Fate of pyruvate generated during glycolysis is dependent on presence of oxygen. What happens with adequate or inadequate O2?
Adequate O2: Pyruvate–>Acetyl CoA
Inadequate O2: Pyruvate–>Lactate (increase lactate–>metabolic acidosis with compensatory respiratory alkalosis)
pyruvate to acetyl coA produces what?
1 NADH, 1 CO2
Function of ALT and cofactor
Alanine aminotransferase (B6): alanine carriers amino groups to liver from muscle
Function of PC and cofactor
Pyruvate carboxylase (biotin): oxaloacetate can replenish TCA cycle or be used in gluconeogenesis
function of Pyruvate dehdyrogenase and cofactor
(B1, B2, B3, B5, lipoic acid): transition from glycolysis to TCA cycle
Function of lactic acid dehydrogenase and cofactor
(B3): end of anaerobic glycolysis–>major pathway in RBC, WBC, cornea, lens, testes, kidney medulla
Function of lipoic acid
Serves in decarboxylation of alpha ketoacids and transfer of alkyl groups (ie. from pyruvate to coenzyme A)
Oxaloacetate–>Citrate
Citrate synthase
Isocitrate–>alphaketogluctarate
Isocitrate dehydrogenase
Alphaketoglutarate–>succinyl-coA
alpha ketoglutarate dehydrogenase.
Krebs pneumonic and what it generates for each acetyl coA
3 NADH, 1 FADH2, 2 CO2, 1 GTP “Citrate Is Krebs Starting Substrate For Making Oxaloacetate”
Complex 4
cytochrome c oxidsase
Complex 3
Coenzyme q
Complex 2
succinate dehydrogeniase
Block complex I
Rotenone
Bock complex III (coenzyme q)
Antimycin A
Block complex IV (cytochrome c oxidase)
Cyanide, CO
Block complex V (ATP synthase)
Oligomycin
Uncoupling agents
2,4 dinitrophenol, aspirin, thermogenin in brown fat (produces heat)
Glucocorticoids are potent stimulators of gluconeogenesis and specifically increase what two enzymes
Phosphoenol pyruvate carboxykinase and glucose 6 phosphatase
Difference between odd chain fatty acids and even chain fatty acids in glucose source?
Odd chain fatty acids can be converted to propionyl CoA during metabolism, which can enter the TCA cycle (as succinyl-coA) and undergo gluconeogenesis, and serve as glucose source
Even chain fatty acids cannoot produce new glucose, since they yield only acetyl-CoA equivalents.
Predominant source of carbon atoms for glucose synthesis during gluconeogenesis?
Lactate
What is pyruvate derived from in gluconeogenesis?
Lactate, glycerol, glucogenic AA (eg. alanine)
HMP shunt main job
Provide NADPH
Oxidative HMP shunt pathway
Glucose 6-phosphate–>Ribulose 5 phosphate, 2 NADPH, CO2 via Glucose 6 phosphate dehydrogenase
Non-oxidative HMP shunt pathway
Ribulose5-PhosphateRibose 5 phosphate, Glyceraldehyde 3 phosphate, Fructose 6 phosphate via transketolases and phosphopentose isomerase
Oxidizing agents that can percipitate G6PD deficiency?
“Spleen Purges Nasty Inclusions From Damaged Cells”->Sulfonamides, Primaquine, Nitrofurantoin, Isoniazid, Fava Beans, Dapsone, Chloroquine
With fructokinase deficiency, what is primary method of metabolism of fructose to fructose 6-phosphate?
Hexokinase
Urine dipstick tests for what sugar in blood?
Glucose only!!
Why do symptoms arise in fructose intolerance?
fructose 1-p is trapped and usage of all fructose prevents glycogenolysis and gluconeogenesis causing hypoglycemia. Also see jaundice, cirrhosis (hepatocellular manifestations)
Alcohol counterpart of glucose?
Sorbitol (converted from glucose via aldose reductose)
Tissues with aldose reductase and sorbitol dehydrogenase
Liver, ovaries, seminal vesicles, very low levels of sorbitol dehydrogense in lens
Tissues with aldose reductase only
Schwann cells, kidney, retina
Essential amino acids (need to be supplied in diet)
“PVT TIM HALL” Phenylalanine, Valine, Threonine, Tryoptophan,, Isoleucine, Methionine, Histidine, Arginine (considered essential for children because needed during periods of growth), Lysine, Leucine
Acidic AA (negatively charged at body pH)
Aspartic acid (ie. aspartate) , glutamic acid (ie glutamate)
Basic AA
Arginine (most basic), Lysine, Histidine
pH>pKa
protons dissociate from amino acids
pH
proton associate to group on amino acids
Lactase deficiency stool and breath tests?
decrease pH stool and increase hydrogen content in breath
Two AA required during periods of growth
Arginine and histidine
Urea’s nitrogen is derived from what?
Aspartate and NH3
Urea cycle pneumonic
Ordinarily, Careless Crappers Are Also Frivilous About Urination
Two major carriers of nitrogen from tissues?
Alanine and glutamine
Acidify GI tract and trap NH4+ for excretion
Lactulose
Decrease colonic ammoniagenic bacteria
Rifaximin
(Both of these bind AA and lead to excretion) may be given to decrease ammonia levels
Benzoate or Phenylbutyrate
Ornithine transcarbamylase deficiency
X-linked recessive (vs other urea cycle deficiencies, that are auto recessive)
Cofactor used in hydroxylase enzymes in synthesis of tyrosine, DOPA, serotonin, NO
BH4
Phenylalanine and derivatives
Phe–>Tyrosine (converted to thyroxine)–>DOPA (which is converted to melanin)–>Dopamine–>Epi–>NE
Tryptophan and derivatives
Serotonin, Niacin
Histidine and derivative
Histamine
Glutamate and derivitives
GABA and Glutathione
Glycine and deriviatives
Porphyrin–>Heme
Arginine and derivitives
NO, Urea, Creatinine
PKU mutated enzyme
Phenylalanine hydroxylase
MSUD mutated enzyme
alphaketoacid dehydrogenase
Mutated enzyme albinism
tyrosinase
mutated enzyme alkaptonuria
Homogentisate oxidase
NE and dopamine is produced by _____, while epinephrine is only produced by _______
CNS and ANS, adrenal gland
First step in catecholamine synthesis in adrenal medulla:
Tyrosine–>DOPA via tyrosine hydroxylase
Failure to absorb what AA in cystinuria
Cysteine, ornithine, lysine, arginine (COLA)
alpha 1,4 glycosidic linkage to glycogen chain is broken down to?
Glucose 1-P via glycogen phosphorylase
alpha 1,6 glycosidic linkage is borken down to?
glucose via alpha 1,6 glucosidase
Glycogen–>Glucose 1-Phosphate
Glycogen phosphorylase
Glucose 1-Phosphate–>Glucose 6-phosphate
Phosphoglucomutase
Glucose 6-Phosphate–>Glucose
Glucose 6-phosphatase (only in liver)
alpha 1,6 glucosidase function?
alpha 1,6 glycosidic linkage –>glucose
Von Gierke deficiency+treatment
Pompe deficiency
Cori dificiency
McArdle deficiency
Glucose-6-Phosphatase, glucose/cornstarch at night; avoidance of fructose+galactose
Lysosomal alpha 1,4 glucosidase (acid maltase)
Debranching enzyme (alpha 1,6-glucosidase)
Skeletal muscle Glycogen phosphorylase (myophosphorylase), Treat w/ vitamin B6 (cofactor)
Fabry disease
Symptoms
Deficient enzyme?
Accumulated substrate?
Symptoms: Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease
alpha-galactosidase A
Ceramide trihexoside
Gaucher disease
Symptoms
Deficient enzyme?
Accumulated substrate?
Symptoms: Hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femur, bone crises, Gaucher cells,
Glucocerebrosidase (B-glucosidase)
Glucocerebroside
Niemann-Pick
Symptoms
Deficient enzyme?
Accumulated substrate?
Progressive neurodegeneration, hepatosplenomegaly, foam cells (lipid-laden macrophages), “cherry-red” spot on macula
Sphingomyelinase
Sphingomyelin
Tay-sachs disease
Symptoms
Deficient enzyme
accumulated substrate
Progressive neurodegneration, no hepatosplenomegaly, developmental delay, “cherry-red” spot on macula, lysososmes with onion skin
B-hexosaminidase A
GM2 ganglioside
Krabbe disease
Symptoms
Deficient enzyme
accumulated substrate
Peripheral neuropathy, developmental delay, optic atrophy, globoid cells
Galactocerebrosidase
Galactocerebroside
Psychosine
Metachromatic leukodystrophy
Symptoms
Deficient enzyme
Accumulated substrate
Central and peripheral demyelination with ataxia, dementia
Arylsulfatase A
Cerebroside sulfate
Hurler syndrome
Symptoms
Deficient enzyme
Accumulated substrate
Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly
Alpha-l-iduronidase
Heparan sulfate, dermatan sulfate
Hunter syndrome
Symptoms
Deficient enzyme
accumulated substrate
Mild hurler +aggressive behavior, NO corneal clouding
Iduronate sulfatase
Heparan sulfate, dermatan sulfate
Rate limiting enzyme in fatty acid synthesis
acetyl coA carboxylase
Rate limiting enzyme in LCFA degradation
Carnitine acyltransferase I
Predominant location of fatty acid synthesis
liver, lactating mammary glands, adipose tissue
What is the difference in odd chain fatty acid and even chain fatty acid production?
Odd chain fatty acids yield 1 propionyl coA which enter TCA cycle as succinyl coA, undergo gluconeogenesis and serve as glucose source
Even chain fatty acids cannot produce new glucose, since they yield only acetyl-coA equivalents
What is the only TAG component from odd chain FFA that contributes to gluconeogenesis?
propionyl-coA
Only organ that can use glycerol for energy
liver
Type I hyperchylomicronemia deficiency
lipoprotein lipase deficiency or altered apolipoprotein CII
Type IIa familial hypercholesterolemia deficiency
LDL receptor deficiency
Type IV hypertriglyceridemia deficiency
Hepatic overproduction of VLDL
