Week Two Objectives

Question 1

What does hormone sensitive lipase do?

Answer 1

liberates a fatty acid from glycerol in adipocyte

Activated by: glucagon, epinephrine, and norepinephrine

Inhibited by: insulin

Question 2

What does Fatty Acyl CoA Synthetase do?

Answer 2

adds CoASH to a fatty acid to make Fatty Acyl CoA (different synthestases for different length chains)

Question 3

How do fatty acids enter the inner mitochondrial matrix for beta oxidation?

Answer 3

The carnitine shuttle

Carnitine palmitoyl transferase 1 (CPT1) takes off acetyl coA and add carnitine (malonyl CoA is an allosteric inhibitor)

One carnitine is added it can be transported across inner mitochondrial membrane through anti-port with a carnitine molecule

One in inner mitochondrial matrix CPT II takes off carnitine and adds aetyl CoA from mitochondrial pool

Question 4

Describe the process of beta-oxidation

Answer 4

1. Oxidation by Acyl-CoA dehyrdogenase, electrons transferred from alpha carbon to FAD to make FADH2
2. Hydration by enoyl-CoA hydrase (H20 saturates double bond adding alcohol to the beta carbon)
3. Oxidation by Hydroxyacyl-CoA dehydrogenase (alcohol on beta carbon gets oxidized to make double bond between them)

Question 5

Altered metabolism in cancer

Answer 5

Warburg effect

PK-M2 varients bind another molecule that boots off the activator decreasing enzyme activity so glycolysis intermediate can be utilized by growing cell

Question 6

Lactic acidosis

Answer 6

Lactate dehydrogenase converts pyruvate to lactate under anaerobic conditions

Lactic Acidosis- accumulation of lactic acid from glycolysis under anaerobic condition can lower pH of tissues/ blood

Question 7

What is medium chain acyl-CoA dehydrogenase deficiency?

Answer 7

Inability to oxidize medium chain fatty acids in the first step of beta oxiation

Symptoms: Reye syndrome, fasting hypoketotic hypoglycemia, hepatic ancephalopathy, SIDS

Diagonse by lipid profile in blood and indentification of mutations

Question 8

Jamaican Vomiting Sickness

Answer 8

From unripe ackee fruit, which contains inhibitor for short and medium chain acyl-CoA-dehydrogenase

Question 9

Carnitine Palmitoyl Transferase II deficiency

Answer 9

unable to take of carnitine to add acetyl Co A

elevated fatty acids in blood, and elevated acylcarnitine

autosomal recessive, muscle pain and weakness and myglobinuria after prolonged exercise

Question 10

How and why does 2,3 bisphosphoglycerate divert from glycolysis?

Answer 10

2,3 BPG in RBC regulates oxygen delievery

It displaces oxygen from hemoglobin and stabilizes deoxyhemoglobin

Lack of O2 halts ETC, backs up glycolysis, increases [3-phophoglycerate]

3-phosphoglycerate then gets converted to 2,3 BPG which increases oxygen delivery to tissues

Question 11

What are ketone bodies?

Answer 11

Body’s normal response to starvation

Decreased insulin/glucgon ratio stimulates hormone sensitive lipase to free fatty acids

FA cannot cross blood-brain barrier, liver responds by cleaving glycogen , when thats depleated coverts to ketone synthesis.

Question 12

Describe the process of ketone synthesis

Answer 12

Increased levels of B-oxidation in liver result in lots of NADH + H and acetyl CoA

This drives TCA backwards, oxaloacetate is converted to malate, malate leaves TCA for gluconeogenesis

Less oxaloacetate diverts acetyl CoA to ketone body synthesis, acetone is byproduct and is exhaled

Excessive ketone production leads to ketoacidosis (drop in blood pH)

*In hypoglycemic patient, abscence of elelvated ketone bodies suggests defect in fatty acid metabolism such as MCAD*

Question 13

Describe the significance of special cases of fatty acid catabolism: the breakdown of odd chain length and branched chain fatty acids, oxidation of unsaturated fatty acids, and peroxisomal oxidation

Answer 13

Unsaturated fatty acids- get less energy, loose a little energy for each point of unsaturation

Odd chain fatty acids- left with 3 carbon fatty acid (Propionyl CoA which can enter TCA at 6 oclock

Long chain fatty acids- (more that 22 carbons) degraded in peroxisomes. Similar process but transfers electrons to molecular oxygen and then creates peroxide all the way down to short chain and then transferred to mitochondria

Branched Chain Fatty acids- humans can’t make but plants can, makes cuts to get acetyl CoA and propinal CoA

Question 14

What does pyruvate dehydrogenase do?

Answer 14

Links glycolysis and TCA cycle

Question 15

What are the functions of the TCA cycle?

Answer 15

1. Oxidize 2 Carbons from acetate to CO2
2. Reduce NADH and FADH2, generate GTP
3. Generate precursors for biosynthesis