USMLE (Fach) / Biochemistry - Metabolism (Lektion)
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- How is acetyl-CoA ultimately converted into fatty ... Acetyl-CoA → malonyl CoA (step requires biotin cofactor) → fatty acids
- How is acetyl-CoA ultimately converted into β-hydroxybutyrate? ... Acetyl-CoA → acetoacetyl-CoA → HMG-CoA → acetoacetate → β-hydroxybutyrate
- How is acetyl-CoA ultimately converted into cholesterol? ... Acetyl-CoA → acetoacetyl-CoA → HMG-CoA → mevalonate (via HMG-CoA reductase) → cholesterol
- Starting with acetyl-CoA, outline all of the steps ... Acetyl CoA and oxaloacetate → citrate → isocitrate → α-ketoglutarate → succinyl-CoA → succinate → fumarate → malate → oxaloacetate
- Outline the steps in the conversion of pyruvate into ... Pyruvate → oxaloacetate via pyruvate carboxylase and oxaloacetate → phosphoenolpyruvate via PEP carboxykinase
- Fructose can enter glycolysis by 2 pathways. Outline ... Fructose → fructose-1-phosphate (via fructokinase) → either DHAP or glyceraldehyde → glyceraldehyde-3-P (both via aldolase B)
- Glucose-6-phosphate must undergo a reaction before ... Dephosphorylation via glucose-6-phosphatase into glucose; von Gierke disease
- Which 2 enzymes are responsible for ultimately converting ... Galactose → galactose-1-phosphate via galactokinase; galactose-1-phosphate → glucose-1-phosphate via galactose-1-phosphate uridyltransferase
- Outline the steps by which glucose-6-phosphate may ... Glucose-6-phosphate → glucose-1-phosphate → UDP-glucose → glycogen
- The 2 enzymes for converting galactose into glucose-1-phosphate ... Galactokinase deficiency (1st step): mild galactosemia; galactose-1-phosphate uridyltransferase deficiency (2nd step): severe galactosemia
- The 2 enzymes for converting fructose into DHAP/glyceraldehyde ... Fructokinase deficiency (1st step): essential fructosuria (mild); aldolase B (2nd step): fructose intolerance (severe)
- Triglyceride metabolism byproducts can ultimately ... Triglyceride metabolism releases glycerol, which is converted into DHAP that becomes either glyceraldehyde-3-P or fructose-1,6-bisphosphate
- Argininosuccinate is converted into 2 different products ... Fumarate (enters the TCA cycle) and arginine (remains in the urea cycle)
- Starting with CO2 and NH3, outline all of the steps ... CO2 and NH3 → carbamoyl phosphate → citrulline (requires ornithine) → argininosuccinate → arginine (and fumarate) → ornithine (+ H2O → urea)
- ATP production Aerobic metabolism of glucose produces 32 net ATP via malate-aaspartate shuttle (heart and liver), 30 net ATP via glycerol-3-phosphate shuttle (muscle). Anaerobic glycolysis produces only 2 net ATP per ...
- Hexokinase vs glucokinase Phosphorylation of glucose to yield glucose-6-phosphate is catalyzed by glucokinase in the liver and hexokinase in other tissues. At low glucose concentrations, hexokinase sequesters glucose in the tissue.At ...
- In glycolysis, which reactions generate ATP? Conversions of 1,3-bisphosphoglycerate to 3-phosphoglycerate and phosphoenolpyruvate to pyruvate
- Regulation by fructose-2,6-bisphosphate FBPase-2 (fructose bisphosphatase-2) and PFK-2 (phosphofructokinase-2) are the same bifunctional enzyme whose function is reversed by phosphorylation by protein kinase A. Fasting state: ↑ glucagon ...
- Pyruvate dehydrogenase complex Mitochondrial enzyme complex linking glycolysis and TCA cycle. Pyruvate + NAD+ + CoA → Acetyl-CoA + CO2 + NADH Complex contains 3 enzymes that require 5 cofactors:1. Thiamine pyrophosphate (B1)2. Lipoic ...
- Pyruvate metabolism 1. Alanine aminotransferase (B6): alanine carries amino groups to the liver from muscle 2. Pyruvate carboxylase (biotin): oxaloacetate can replenisch TCA cycle or be used in gluconeogenesis 3. Pyruvate ...
- TCA cycle (Krebs cycle) The TCA cycle produces 3 NADH, 1 FADH2, 2 CO2, 1 GTP per acetyl-CoA = 10 ATP/acetyl-CoA (2x everything per glucose) - Reactions occur in the mitochondria
- Electron transport chain and oxidative phosphorylation ... NADH electons from glycolysis enter mitochondria via the malate-aspartate or glycerol-3-phosphate shuttle. FADH2 electrons are transferred to complex II (succinate dehydrogenase). Electron transport inhibitors: ...
- HMP shunt (pentose phosphate pathway) Provides a source of NADPH from abundanty available glucose-6-phosphate (NADPH is required for reductive reactions, eg, glutathione reduction inside RBCs, respiratory burst, the cytochrome P-450 system, ...
- Glucose-6-phosphate dehydrogenase deficiency NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides. ↓ NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents (eg, ...
- Disorders of fructose metabolism Essential fructosuria: Defect in fructokinase.- Autosomal-recessive- Benign and asymptomatic, since fructose is not trapped in cells.- Hexokinase becomes 1° pathway for converting fructose to fructose-6-phosphate.- ...
- Disorders of galactose metabolism Galactokinase deficiency: Hereditary deficiency of galactokinase.- Autosomal-recessive - Galactitol accumulates if galactose is present in diet.- Relatively mild condition.- Symptoms: galactose appears ...
- Lactase deficiency Insufficient lactase enzyme → dietary lactose intolerance. Lactase functions on the intestinal brush boarder to digest lactose into glucose and galactose. - Primary: age-dependent decline after childhood ...
- Which are the 2 energy-requiring steps in the urea ... CO2 + NH3 to carbamoyl phosphate via carbamoyl phosphate synthetase I (2 ATP) and aspartate + citrulline to argininosuccinate (1 ATP)
- Hyperammonemia Can be acquired (eg, liver disease) or hereditary (eg, urea cycle enzyme deficiencies). - Presents with flapping tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring ...
- Ornithine transcarbamylase deficiency - Most common urea cycle disorder.- X-linked recessive (vs other urea cycle enzyme deficiencies, which are autosomal recessive). - Interferes with the body's ability to eliminate ammonia.- Often evident ...
- Arginine derivatives? Arginine → Creatinine Arginine → Urea Arginine → Nitric oxide
- Phenylalanine derivatives Phenylalanine (+BH4) → Tyrosine (+BH4) → Dopa (+B6) → Dopamine (+Vitamin C) → Norepinephrine (+SAM) → Epinephrine Tyrosine → Thyroxine Dopa → Melanin
- Tryptophan derivatives Tryptophan → Niacin → NAD/NADH Tryptophan → Serotonin → Melatonin
- Catecholamine synthesis/catabolism Phenylalanine (+ BH4) → Tyrosine (+BH4) → Dopa (+ B6) → Dopamine (+ Vit. C) → Norepinephrine (+ SAM)→ Epinephrine Tyrosine → Homogentisic acid → Maleylacetoacetic acid → Fumarate → ...
- Phenylketonuria Due to ↓ phenylalanine hydroxylase or ↓ tetrahydrobiopterin (BH4) cofactor (malignant PKU).- Tyrosine becomes essential- Autosomal-recessive. Incidence ±1:10,000- Screening occurs 2-3 days after ...
- Maple syrup urine disease Blocked degradation of branched amino acids (isoleucine, leucine, valine) due to ↓ branched-chain α-ketoacid dehydrogenase (B1). - Autosomal recessive - Causes ↑ α-ketoacids in the blood, especially ...
- Alkaptonuria Congenital deficiency of homogentisate oxidase in the degradative pathway of tyrosine to fumarate → pigment-forming homogentisic acid accumulates in tissue- Autosomal recessive- Usually benign Findings:- ...
- Homocytinuria - Autosomal recessive Causes:- Cytathionine synthase deficiency (treatment: ↓ methionine, ↑ cysteine, ↑ B6, B12, and folate in diet)- ↓ Affinity of cystathionine synthase for pyridoxal phosphate ...
- Cystinuria Defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of cystine, ornithine, lysine and arginine.- Autosomal recessive. - Common (1:7000) - Excess cystine in the urine can ...
- Glycogen Branches have α-(1,6) bonds; linkages have α-(1,4) bonds. Skeletal muscle: Glycogen undergoes glycogenolysis → glucose-1-phosphate → glucose-6-phosphate Hepatocytes: Glycogen is stored and undergoes ...
- Lysosomal storage diseases - Sphingolipidoses Fabry disease (X-linked recessive)- Deficient enzyme: α-galactosidase A- Accumulated subsstrate: Ceramide trihexoside (globotriaosylceramide)- Presents during childhood or adolescence.- Early findings: ...
- Fatty acid metabolism Fatty acid synthesis requires transport of citrate from mitochondria to cytosol. Predominantly occurs in liver, lactating mammary glands, and adipose tissue.Citrate → citrate shuttle into cytoplasm ...
- Ketone bodies In the liver, fatty acids and amino acids are metabolized to acetoacetate and β-hydroxybutyrate (to be used in muscle and brain) In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted ...
- Apolipoproteins Apolipoprotein E:- Mediates remnant uptake by the liver- on chylomicron, chylomicron remnant, VLDL, IDL, HDL- not on LDL Apolipoprotein A-I:- Activates LCAT- on chylomicron, HDL Apolipoprotein C-II:- ...
- Familial dyslipidemias I - Hyperchylomicronemia- Autosomal-recessive- Lipoprotein lipase or apolipoprotein C-II deficiency- ↑ chylomicrons, TG, cholesterol- Pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas ...
- Metabolism sites Mitochondria: Fatty acid oxidation (β-oxidation), acetyl-CoA production, TCA cycle, oxidative phosphorylation, ketogenesis. Cytoplasm: Glycolysis, HMP shunt, and synthesis of steroids (SER), proteins ...
- Rate-determining enzymes of metabolic process Glycolysis: Phosphofructokinase-1- AMP ⊕, fructose-2,6-biphosphate ⊕- ATP Θ, Citrate Θ Gluconeogenesis: Fructose-1,6-biphosphatase- Citrate ⊕- AMP Θ, fructose-2,6-biphosphate Θ TCA cycle: ...
- Arsenic - Arsenic inhibits lipoic acid. Clinical findings: - Pigmentary skin changes- Skin cancer- Vomiting - Diarrhea containing blood- QT prolongation
- Pyruvate dehydrogenase complex deficiency Causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (ALT). - X-linked Findings:- Neurologic defects- Lactic acidosis- ↑ serum alanine starting in infancy Treatment: ↑ ...
- Gluconeogenesis, irreversible enzymes Pyruvate carboxylase: In mitochondria. Pyruvate → oxaloacetate.- Requires biotin, ATP. Activated by acetyl-CoA. Phosphoenolpyruvate: In cytosol. Oxaloacetate → phosphoenolpyruvate.- Requires GTP. ...