RQ2.Answer = E. The irreversible, oxidative portion of the pentose phosphate pathway provides the nicotinamide adenine dinucleotide phosphate (NADPH) that supplies the reducing equivalents needed for activity of cytochrome P450 (CYP) proteins and for the regeneration of functional (reduced) glutathione. It is also an important source of NADPH for reductive biosynthetic processes in the cytosol, such as FA and cholesterol synthesis. [Note: Malic enzyme is another source.] CYP proteins are monooxygenases (mixed-function oxidases). They incorporate one O atom from O2 into the substrate as the other is reduced to water. It is the CYP proteins of the smooth endoplasmic reticular membrane that are involved in detoxification reactions. Those of the inner mitochondrial membrane are involved in the synthesis of steroid hormones, bile acids, and vitamin D. Reactive oxygen species are reduced by glutathione peroxidase as glutathione is oxidized. RQ3.Answer = C. Serotonin is released by activated platelets and causes vasoconstriction and platelet aggregation. [Note: Platelets do not synthesize serotonin, but they take up that which was made in the intestine and secreted into the blood.] Serotonin is associated with a feeling of well-being. It is degraded to 5-hydroxyindoleacetic acid by monoamine oxidase that catalyzes oxidative deamination. It is catechol-O-methyltransferase that catalyzes the methylation step in the degradation of the catecholamines. Serotonin is synthesized from tryptophan in a two-step process that utilizes tetrahydrobiopterin (BH4) requiring tryptophan hydroxylase and a pyridoxal phosphate (PLP)-requiring decarboxylase (see figure at right). RQ4.Answer = B. The exocrine pancreas secretes enzymes required for the digestion of dietary carbohydrate, protein, and fat. The endocrine pancreas secretes the peptide hormones insulin and glucagon. Damage that affects the functions of the pancreas would lead to diabetes (decreased insulin) and steatorrhea (fatty stool), with the latter the consequence of maldigestion of dietary fat. As was seen with the rise of troponins in a myocardial infarction and transaminases in liver damage, loss of cellular integrity (as would be seen in autodigestion of the pancreas) results in proteins that normally are intracellular being found in higher-than-normal concentrations in the blood. Secretin causes the pancreas to release bicarbonate to raise the pH of the chyme coming to the intestine from the stomach. Pancreatic enzymes work best at neutral or slightly alkaline pH. Pancreatitis is seen in individuals with hypertriglyceridemia as a result of a deficiency in lipoprotein lipase or its coenzyme, apolipoprotein C-II.
Case 4: Answers to Thought Questions
TQ1.A. The rise in cytosolic NADH seen with ethanol metabolism inhibits glycolysis. The glyceraldehyde 3-phosphate dehydrogenase step requires NAD+, which gets reduced as glyceraldehyde 3-phosphate gets oxidized. With the rise in NADH, glyceraldehyde 3-phosphate accumulates.