(a) Highlight role of various hormones in the regulation of digestive secretions. (10 marks) (b) Describe the balance sheet of…

(a) Hormones regulating digestive secretions

Gastrin: released by G cells of the stomach antrum when food, peptides and stretch are sensed. It stimulates the parietal cells to secrete HCl and the chief cells to secrete pepsinogen, and also stimulates gastric motility. Secretin: released by S cells of the duodenum when acid chyme arrives. It stimulates pancreatic duct cells to secrete watery juice rich in bicarbonate that neutralises the acid, and reduces gastric acid secretion. Cholecystokinin (CCK): released by I cells of the duodenum in response to fats and proteins. It stimulates the pancreas to secrete enzymes and makes the gall bladder contract, and relaxes the sphincter of Oddi so that bile and juice flow into the duodenum. It slows gastric emptying. Gastric inhibitory peptide (glucose-dependent insulinotropic peptide): released by K cells on fat and glucose in the duodenum. It inhibits gastric secretion and motility and stimulates insulin release. Enterocrinin and vasoactive intestinal peptide stimulate the secretions of the intestinal glands.

(b) Balance sheet of ATP production in glycolysis

Glycolysis converts one glucose to two pyruvate in the cytosol. ATP used (investment phase): two ATP, one by hexokinase (glucose to glucose-6-phosphate) and one by phosphofructokinase (fructose-6-phosphate to fructose-1,6-bisphosphate). ATP formed (pay-off phase): four ATP, by substrate-level phosphorylation. Two are formed by phosphoglycerate kinase (1,3-bisphosphoglycerate to 3-phosphoglycerate) and two by pyruvate kinase (phosphoenolpyruvate to pyruvate), because every step after the splitting occurs twice. Net gain: 4 − 2 = 2 ATP per glucose. NADH: glyceraldehyde-3-phosphate dehydrogenase makes 2 NADH. Under aerobic conditions these give about 3 to 5 ATP through the respiratory chain, depending on the shuttle (glycerol phosphate or malate-aspartate), which makes the aerobic total about 30 to 32 ATP when pyruvate is oxidised completely. In anaerobic conditions NADH is used to make lactate and only the net 2 ATP is gained.

(c) Acrosome reaction during fertilisation

The acrosome is a cap-like vesicle over the sperm nucleus that holds hydrolytic enzymes (hyaluronidase, acrosin). The acrosome reaction is the release of these enzymes when the sperm meets the egg, and it prepares the sperm for entry. Step 1: Capacitated sperm penetrate the cumulus cells, aided by hyaluronidase. Step 2: The sperm binds the glycoprotein ZP3 of the zona pellucida, which causes calcium to enter the sperm. Step 3: The outer acrosomal membrane fuses with the plasma membrane at many places, and the enzymes are released by exocytosis. Step 4: Acrosin digests a path through the zona, and the sperm reaches the egg membrane, where its membrane fuses with that of the egg. Step 5: Egg activation follows, with the release of cortical granules to block entry of other sperm (polyspermy). The reaction is species-specific.

(d) Neurotransmitters and the neuromuscular junction

List of neurotransmitters: Acetylcholine. Amines: noradrenaline, adrenaline, dopamine, serotonin and histamine. Amino acids: glutamate, GABA and glycine. Neuropeptides: substance P, enkephalins and endorphins. Others: nitric oxide and ATP. Acetylcholine at the neuromuscular junction: Step 1: A nerve impulse opens calcium channels in the terminal of the motor neuron, so vesicles release acetylcholine into the synaptic cleft. Step 2: Acetylcholine binds nicotinic receptors on the motor end plate of the muscle fibre, which opens sodium channels. Step 3: The resulting end-plate potential starts a muscle action potential that leads to contraction. Step 4: Acetylcholinesterase quickly breaks down acetylcholine, so that the muscle relaxes and the junction is ready for the next signal. Blocking of receptors by curare or loss of receptors in myasthenia gravis causes paralysis or weakness.

(e) Competitive and non-competitive enzyme inhibition

Competitive inhibition: The inhibitor resembles the substrate and binds reversibly to the active site, so the two compete. Raising the substrate concentration overcomes the inhibition. Vmax is unchanged and Km increases. In a Lineweaver-Burk plot the lines meet at the same point on the y-axis. Example: malonate inhibits succinate dehydrogenase, and methotrexate inhibits dihydrofolate reductase. Non-competitive inhibition: The inhibitor binds to a site other than the active site, on the free enzyme or on the enzyme-substrate complex, which changes the shape of the enzyme. Substrate cannot reverse it. Vmax falls and Km is unchanged. In the double reciprocal plot the lines meet on the x-axis. Example: heavy metals such as mercury and lead, and cyanide acting on cytochrome oxidase.