32: INTEGRATION OF METABOLISM

Question 1

ketogenesis

Answer 1

• ketone body synthesis in the liver in mit.matrix
• way of using acetyl CoA; start w/ 2
• end up w/ acetoacetate/acetone/ß-hydroxy-butyrate transported to other tissues
• ß-ox of fats; acetyl CoA; ox in TCA cycle; but need oxaloacetate
• carbohydrates low when ox. fats so some oxaloacetate is used in gluconeogenesis so not enough for acetyl CoA to enter TCA cycle so some acetyl CoA is used to make ketone bodies; can be used as alternative fuel source in other tissues eg. heart muscle

-in starvation, increased synthesis of ketone bodies; brain can adapt to use ketones instead of glucose

Question 2

type 1 diabetes

Answer 2

-insulin is absent; glucagon remains high; stimulates gluconeogenesis in the liver; all oxaloacetate is used to make glucose even if blood glu is high so acetyl coA has to be used to make ketone bodies

Question 3

glyoxylate pathway

Answer 3

• mammals can’t make glucose from acetyl coA
• plants and bacteria can
• isocitrate lyase and malate synthase enzymes
• net 1 molecule of malate thus oxaloacetate generated

Question 4

cholesterol synthesis

Answer 4

• cholesterol needed for cell membranes/to make steroid hormones
• complicated ring structure; build up entirely from acetyl coA
• start w/3x acetyl coA to give activated isoprene unit; many fold up to form squalene; eventually forms cholesterol

Question 5

committed step of cholesterol synthesis

Answer 5

• cat by HMG-CoA reductase which uses NADPH to reduce HMG-CoA to mevalonate
• before this step HMG-CoA could be used to make ketone bodies
• enzyme inhibited by statins; important cholesterol lowering drugs;

Question 6

glu-6-P

Answer 6

=back to glucose in liver
-used to make other sugars e.g. glucosamine or galactose needed for glycosylation of proteins and lipids
=glu-1-P to glycogen
-fru-6-P to pyruvate
-6-phosphogluconate to ribose-5-P

Question 7

pyruvate and acetyl CoA

Answer 7

=alanine via transamination
=lactate
-oxaloacetate for gluconeogenesis to glu-6-P to pyruvate
-acetyl coA:
=fatty acids
=amino acids
-CO2 (ox in TCA cycle)
-HMG-CoA - cholesterol/ketone bodies

Question 8

control of metabolism

Answer 8

-energy state or response to hormones

Question 9

Effect of glucagon (low blood glucose)

Answer 9

• IN glycogen breakdown (IN glycogen phosphorylase); DE glycogen synthesis (DE glycogen synthase)
• DE glycolysis (DE PFK1); IN gluconeogenesis (IN fru-1,6-bisP; DE pyruvate kinase)
• IN fatty acid mobilization (IN triacylglycerol lipase)

Question 10

effects of insulin (high blood glucose)

Answer 10

• IN glucose uptake (IN glucose transporter/glucokinase)
• IN glycogen synthesis (IN glycogen synthase)
• DE glycogen breakdown (DE glycogen phosphorylase)
• IN glycolysis/acetyl CoA production (IN PFK1/PDH)
• IN fatty acid synthesis (IN acetyl CoA carboxylase)
• IN triacylglycerol synthesis (IN lipoprotein lipase)

-PFK1 and fru-1,6-bisP indirect activation

Question 11

glucose transporter

Answer 11

• transport protein which takes glu into the cell
• in muscles/adipose tissue; GluT4 is insulin dependent
• presynthesized protein; sequestered in intracellular vesicles; insulin causes it to go to cell surface
• liver uses GluT2 not insulin dependent
• brain/redbloodcells GluT1 also not insulin dependent