Lipids 1 Flashcards
Energy from Fat
cells get 2.5x amount of ATP from degradation of fat when compared to glycogen (9kcal/g vs. 4kcal/g)
2 Classes of Essential FA’s
omega-3 (linolenic acid) and omega 6 (linoleic acid)
How do FA’s get across inner mito membrane?
activated by attaching to CoASH to give acyl-CoA (acyl-CoA synthase [ATP input]), then the acyl group is transferred to carnitine (Carnitine-Palmitoyltransferase I), Acyl-Carnitine can be transported across inner mito membrane by Translocase and then CPTII will transfer acyl back to CoA to give Acyl-CoA
Primary Carnitine Deficiency and other defects in transporting enzymes
genetic defect in acyl-CoA synthase, CPT I or II, translocase; cannot transport FA’s into mito matrix for Beta-oxidation; presents as fasting hypoglycemia; they LIMIT the production of ketone bodies during starvation
Energy Yield from Beta-Oxidation
w/ 16C FA: 8 acetyl-CoA’s and 7 of each NADH and FADH; 80 ATP’s from acetyl-CoA and CAC, 7x1.5 ATP’s for FADH and 7x2.5 ATP’s for NADH = 108 ATP’s - 2 ATP’s
Name enzymes of Beta-Oxidation in Order + reducing equivalents produced
- Acyl-CoA dehydrogenase (FADH formed)
- Enoyl-CoA hydratase
- Hydroxyacyl-CoA dehydrogenase (NADH formed)
- Beta-Ketoacyl-CoA thiolase
When double bonds pose challenge for degradation which enzymes help out?
Enoyl-CoA isomerase (C3=C4)
Reductase (C4=C5)
Besides the mito matrix, where else can Beta-oxidation occur? Differences? Associated Disease?
Peroxisomes of liver and kidney; initial oxidation catalyzed by oxidase system that produces H2O2 INSTEAD of FADH2; ends earlier (8 C’s) and degrades longer FA’s; Zellweger Syndrome associated (CANNOT produce functional peroxisomes)
Acute Fatty Liver
deficiency in long chain hydroxyacyl-CoA dehydrogenase (LCHAD)–accumulation of fat in liver; associated w/ pregnancy
Degradation of Branched FA’s
alpha-oxidation; starts w/ hydroxylation and ends w/ release of CO2
Acyl-CoA Dehydrogenase Deficiencies
very long chain (VLCAD), LCAD, MCAD, SCAD; MCAD most common and presents as non-ketotic hypoglycemia and life threatening
Problems w/ alpha-oxidation of branched FA’s
problems w/ degradation of phytanic acid cause Refsum disease, accumulation of undegraded phytanic acid in blood and tissues cause neuro defects
Peroxisome biogenesis disorders
Zellweger Syndrome; inability to produce functional peroxisomes affects capacity to oxidize very long chain FA’s
What molecule is a precursor for synthesis of ketone bodies in fasting state as well as for cholesterol in well fed state?
HMG-CoA
How does body distribute acetyl-CoA from beta-oxidation? Where does this occur?
Synthesis of Ketone Bodies; occurs in liver and kidneys; ketone bodies can diffuse through membranes and are acidic
Rate Limiting Step of Ketone Body Synthesis
HMG-CoA Lyase; only expressed in liver/kidneys; beta-hydroxy-beta-methylglutaryl-CoA (HMG-CoA)—>Acetoacetate; HMG CoA is COMMITTED to ketone sythesis by HMG-CoA lyase
What happens to Ketone bodies once synthesized?
They (acetoacetate/beta-hydroxybutyrate) diffuse out of liver and kidneys and are converted back into acetyl-CoA; Beta-hydroxybutyrate—>acetoacetate giving NADH; acetoacetate is bonded to CoA w/ succinyl-CoA and the enzyme, acetoacetate:succinyl-CoA transferase, is only expressed OUTSIDE of the liver and kidneys; ensures ketone bodies are only used outside these tissues; Acetoacetyl-CoA splits into 2 molecules of acetyl CoA
