Big Picture Metabolism Review

Question 1

Explain the process of Ketogenesis using intermediates, enzymes, and energy requirements.

Answer 1

1. 2 Acetyl CoA are formed into 1 Acetoacetyl CoA + CoA-SH using 3-Ketoacyl CoA Thiolase
2. Acetoacetyl CoA + Acetyl CoA is made into Hydroxymethylglutaryl-CoA (HMG CoA) using HMG CoA synthase
3. In the liver HMG CoA is cleaved by HMG CoA Lyase to form Acetoacetate and Acetyl CoA.
4. Acetoacetate using Beta Hydroxybutarate Dehydrogenase and NADH can be oxidized to B-Hydroxybutarate. This reaction is reversible.

Question 2

Explain the usage of Ketone Bodies

Answer 2

B-Hydroxybutarate via its dehydrogenase can give NADH and Acetoacetate.

Acetoacetate using ATP, Succinyl-CoA, and Acetoacetate Succinyl-CoA Transferase forms Succinate and Acetoacetyl-CoA.

Acetoacetyl uses 3 Ketoacetyl-CoA Thiolase to make 2 Acetyl-CoA to be used in the citric acid cycle. Gives 21.5 ATP from B-Hydroxybutarate or 19 ATP from Acetoacetate because of the extra NADH. It is one less than expected because we use one ATP when forming Succinate.

Question 3

What are the physiological and non-physiological ketone bodies?

Answer 3

Physiological: B-Hydroxybutarate and Acetoacetate
Non: Acetone

Question 4

Explain Gluconeogenesis

Answer 4

Irreversible Steps: Pyruvate to OAA via pyruvate carboxylase
OAA to Phosphoenol Pyruvate via PEP Carboxykinase
Fructose 1,6 Bisphosphate to Fructose 6 Phosphate via Fructose 1,6 Bisphosphate Phosphatase
Glucose 6 P to Glucose via Glucose 6 P Phosphatase

Pyruvate to OAA in Mitochondrial Matrix. Then shuttled out and rest happens in cytoplasm. CO2 added to pyruvate to make OAA.

Use 6 total ATP equivalents to change 2 pyruvate to Glucose.

Question 5

Explain the Pentose Phosphate Pathway

Answer 5

Glucose 6-P to 6 P Gluconolactone via Glucose 6-P Dehydrogenase also get NADPH
6 P Gluconolacone to 6 P Gluconate
6 P Gluconate to Ribulose 5-P via 6 P Gluconate Dehydrogenase also get NADPH and CO2

In the reversible carbon shuffling step:
Rivulose 5-P can become Ribose 5-P (for nuclei acids), Fructose 6-P, or GA3-P (as intermediates).
Uses Transaldoase, and Transketolase 1 and 2

This reaction is in the cytoplasm with glycolysis. These products can be made any time there isn’t an abundance of NADPH

Question 6

Explain Glycogenesis. Branching as well

Answer 6

Glucose 6-P to Glucose 1-P via Phosphoglucomutase
Glucose 1-P to UDP-Glucose via UDP-Glucose Pyro Phosphorylase

Glycogen synthase takes off UDP and creates a(1,4) bond to glycogen.

Branching enzyme makes the a(1,6) bonds every 8-12 Glucose molecules.

Question 7

Explain Glycogenolysis.

Answer 7

Glucose 1-P is cut from the chain by Phosphorylase and inorganic phosphate. Then can be changed to Glucose 6-P by phosphoglucomutase.

Phosphorylase only cuts up to 4 bonds close to the branching point. Glucotransferase moves the last 3 Glucose to the end of another chain and then Debranching Enzyme cleaves the a(1,6) bond to allow Phosphorylase to continue cleaving.

Question 8

Explain FA Oxidation

Answer 8

First Dehydration: Acyl CoA dehyrogenase adds a double bond and creates 1 FADH2
Hydrations: Enol-CoA Hydrotase adds H2O as an OH and H from double bond.
Second Dehydration: 3-Hydroxyacyl CoA Dehydrogenase makes Carbonyl and creates 1 NADH.
Formation of Acetyl CoA: 3-Ketoacyl CoA Thiolase and SH-CoA cleave one Acetyl CoA from the FA. Gives total of 1 FADH2, 1 NADH, and 1 Acetyl CoA per cycle (2 C)