Correct answer = A. Impaired oxidation of fatty acids <12 carbons in length results in decreased production of acetyl-coenzyme A (CoA), the allosteric activator of pyruvate carboxylase, a gluconeogenic enzyme, and, thus, glucose levels fall. Acetyl CoA can never be used for the net synthesis of glucose. Acetoacetate is a ketone body, and with medium-chain fatty acyl CoA dehydrogenase deficiency, ketogenesis is decreased as a result of decreased production of the substrate, acetyl CoA. Impaired fatty acid oxidation means that less ATP and nicotinamide adenine dinucleotide are made, and both are needed for gluconeogenesis.
6.5. Explain why with Zellweger syndrome both very-long-chain fatty acids (VLCFA) and long-chain phytanic acid accumulate, whereas with X-linked adrenoleukodystrophy, only VLCFA accumulate.
Zellweger syndrome is caused by an inability to target matrix proteins to the peroxisome. Therefore, all peroxisomal activities are affected because functional peroxisomes are unable to be formed. In X-linked adrenoleukodystrophy, the defect is an inability to transport VLCFA into the peroxisome, but other peroxisomal functions, such as α-oxidation, are normal.
Phospholipid, Glycosphingolipid, and Eicosanoid Metabolism 17
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I. PHOSPHOLIPID OVERVIEW
Phospholipids are polar, ionic compounds composed of an alcohol that is attached by a phosphodiester bond to either diacylglycerol (DAG) or sphingosine. Like fatty acids (FA), phospholipids are amphipathic in nature. That is, each has a hydrophilic head, which is the phosphate group plus whatever alcohol is attached to it (for example, serine, ethanolamine, and choline; highlighted in blue in Fig. 17.1A), and a long, hydrophobic tail containing FA or FA-derived hydrocarbons (shown in orange in Fig. 17.1A). Phospholipids are the predominant lipids of cell membranes. In membranes, the hydrophobic portion of a phospholipid molecule is associated with the nonpolar portions of other membrane constituents, such as glycolipids, proteins, and cholesterol. The hydrophilic (polar) head of the phospholipid extends outward, interacting with the intracellular or extracellular aqueous environment (see Fig. 17.1A). Membrane phospholipids also function as a reservoir for intracellular messengers, and, for some proteins, phospholipids serve as anchors to cell membranes. Nonmembrane phospholipids serve additional functions in the body, for example, as components of lung surfactant and essential components of bile, where their detergent properties aid cholesterol solubilization.
II. PHOSPHOLIPID STRUCTURE
There are two classes of phospholipids: those that have glycerol (from glucose) as a backbone and those that have sphingosine (from serine and palmitate). Both classes are found as structural components of membranes, and both play a role in the generation of lipid signaling molecules.
A. Glycerophospholipids