Fatty Acid, Ketone Body, and Triacylglycerol Metabolism (Exam II) Flashcards

Question

For mitochondrial β-oxidation of fatty acids: What reducing equivalents are produced?

Answer 1

FADH2 and NADH. Oxidized by ETC at CoQ and Complex I, respectively, for ATP synthesis; NADH and ATP used in gluconeogenesis

Answer 2

acetyl CoA (from 2C at carboxylate end) oxidized in TCA cycle: CO2, FADH2, NADH, GTP are produced OR used for ketogenesis in liver

Answer 3

Carboxylate to 4C, convert to succinate. 1. Propionyl CoA carboxylate, ATP, biotin & bicarbonate create 4-carbon molecule (L-methylmalonyl CoA) 2. Methylmalonyl CoA mutate, B12 and 5'-deoxyadenosylcobalamin convert to succinyl CoA.

Answer 4

substrate availability: as ↑, β-oxidation ↑ malonyl CoA availability: as ↓, β-oxidation ↑ (since ↑malonyl CoA Ө CAT-1) acetyl CoA/CoA ratio: as ↑, β-oxidation ↓ due to ↓thiolase activity.

Answer 5

Problem: intermediate formed is not a substrate for enoyl hydratase, which requires trans ∆2. Solution: use additional enzyme(s) to convert it to an acceptable substrate. Double bond at odd-numbered C requires 3,2-enoyl CoA isomerase; at even, 2,4-dienoyl CoA reductase Energy yield from unsaturated fa is less than from saturated

Answer 6

~146 ATP (8 ATP/carbon). ATP Yield from oxidation of stearic acid: (18/2 - 1) = 8 NADH = 24 ATP 8 FADH2 = 16 ATP 9 Acetyl CoA: 27 NADH = 81 ATP 9 FADH2 = 18 ATP 9 GTP = 9 ATP Total: 148 Minus 2 ATP: 146 ATP

Answer 7

An additional organelle, the peroxisome, is required for the β-oxidation of VLCFA Only peroxisomes have fatty acyl CoA synthetases for fa > 24C. Differences Transport into peroxisome doesn’t require carnitine and uses an ABC-transporter instead. First oxidative step transfers electrons directly to O2, generating H2O2, so oxidase and not dehydrogenase. Process stops at MCFA (linked to carnitine, not CoA), that go to mitochondria; a chain-shortening process.

Answer 8

occurs at α-C (C-2), not β-C (C-3) and shortens by 1C. Important in the oxidation of branched-chain phytanic acid, a 20C product of chlorophyll degradation in ruminant bacteria; found in milk and animal fat Methyl group on C3 of phytanic acid prevents β-oxidation

Answer 9

Ketone bodies: 4C, H2O-soluble molecules made primarily by liver from the acetyl CoA produced by β-oxidation; used by peripheral tissues to generate acetyl CoA and, ultimately, ATP Synthesis of ketone bodies (in mitochondria of hepatocytes): ketogenesis. Driven by [acetyl CoA]. Presence of HMG-CoA lyase in liver mitochondria allows ketogenesis. Release of CoA supports continued β-oxidation. Use of acetyl CoA keeps acetyl CoA/CoA ratio low in liver so thiolase remains active. The “KB” acetoacetate and β-hydroxybutyrate are organic acids Succinyl CoA transferase is essentially absent from liver, so liver can make but cannot use KB (stops at acetoacetate).

Answer 10

High availability of NADH from β-oxidation pushes acetoacetate to β-hydroxybutyrate. Acetoacetate and Succinyl CoA transferase produce acetoacetyl CoA which undergoes a thiolase to become 2 Acetyl CoA.

Answer 11

X-linked adrenoleukodystrophy (X-ALD, 1:17,000 males): defect in the ABC (ABCD1) transporter that allows entry of VLCFA into peroxisome; childhood and adult forms. In childhood cerebral form, boy develops normally until school age then shows dementia, progressive neurologic loss to a vegetative state, and adrenal insufficiency. Typically fatal by age 10 years. Result in accumulation of VLCFA, especially in brain (but also in adrenals with X-ALD).

Answer 12

Refsum disease (phytanic acid storage disease) is due to a deficiency of the α-hydroxylase AR: see progressive peripheral neuropathy, retinitis pigmentosa, nerve deafness. Signs first seen in teens; full progression can take thirty years. Treatment: dietary restriction of phytanic acid.

Answer 13

Inability to import peroxisomal matrix proteins due to defects in the receptors (PEX proteins) that recognize proteins with peroxisomal targeting sequences. Zellweger syndrome (cerebrohepatorenal syndrome): 1) AR, rare 2) VLCFA accumulate; phytanic acid accumulates 3) severe neurologic defects, progressive hepatic and renal dysfunction, skeletal dysmorphias, facial abnormalities similar to Down syndrome; patients rarely survive first year of life.

Answer 14

ketolysis defects → ketoacidosis Ketoacidosis also seen in untreated type 1 diabetes mellitus: diabetic ketoacidosis or DKA. With DKA the problem is increased production of KB.

Answer 15

Dependence of ketogenesis on mitochondrial β-oxidation: MCAD deficiency Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common defect in mitochondrial fa β-oxidation Typically the patient is less than two years of age with a viral infection that results in decreased appetite. Initially glycogen stores meet the baby’s energy needs. Fats are mobilized but their use is decreased. Ketone body levels remain low. Lethargy and vomiting develop. Glucose levels fall. Lethargy progresses to coma. ~ 20% die during first attack. MCAD is a disorder of fasting adaptation. β-oxidation of fa

Answer 16

ketogenesis defects → hypoketotic hypoglycemia (mitochondrial HMG CoA synthase and lyase) Carnitine deficiency i) decreased synthesis (ex. premature babies) ii) defect in membrane transporter in muscle, heart, kidney; uptake decreased so excretion increased iii) severity varies iv) treatment involves avoidance of fasting, a diet low in LCFA, and dietary supplementation with MCTG and carnitine.

Fatty Acid, Ketone Body, and Triacylglycerol Metabolism (Exam II) Flashcards

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