Lecture 8: Integration of metabolism

Question 1

How does pyruvate serve as an intermediate?

Answer 1

links the metabolism of carbohydrates, lipids, and proteins.

Question 2

What can pyruvate be converted into?

Answer 2

Oxaloacetate, which can be converted to glucose (gluconeogenesis).

Lactic acid by lactate dehydrogenase.

Alanine via transamination.

Acetyl CoA in the mitochondria by pyruvate dehydrogenase.

See figure

Question 3

What metabolic pathways does the TCA cycle link?

Answer 3

Carbohydrates, lipids, and amino acids

Question 4

What is produced in the TCA cycle?

Answer 4

Acetyl CoA

Reduced coenzymes

GTP

ATP (oxidative phosphorylation)

Question 5

What major metabolic precursors can form acetyl CoA?

Answer 5

Pyruvate (from carbohydrates)

Fatty acids (from lipids)

Amino acids (from proteins)

Question 6

What can acetyl CoA be converted into?

Answer 6

Lipids (via fatty acids)

Ketone bodies

Proteins (via amino acids)

Central molecule in the TCA cycle

See figure

Question 7

What can citrate from TCA cycle be used for?

Answer 7

FA synthesis

Question 8

What can oxaloacetate from TCA cycle be used for?

Answer 8

converted to aspartate and used to produce amino acids and nucleic acids

used within the urea cycle

synthesize glucose via gluconeogenesis.

Question 9

What can alpha ketoglutarate from TCA cycle be used for?

Answer 9

transamination reactions by accepting the amino group to synthesize glutamate.

Question 10

What can succinylcholine CoA from TCA cycle be used for?

Answer 10

synthesize haem

Question 11

Conversion of glucose to FAs and TGLs

Answer 11

Glucose -> acetyl CoA, glycerol phosphate

Acetyl CoA is degraded to FAs and acyl-CoA

Acyl CoA combines with glycerol phosphate to form triglycerides

See figure

Question 12

Conversion of glucose to FAs and TGLs

Answer 12

Glucose -> acetyl CoA, glycerol phosphate

Acetyl CoA is degraded to FAs and acyl-CoA

Acyl CoA combines with glycerol phosphate to form triglycerides

TGLs are transported as VLDL to adipose

See figure

Question 13

How are TGLs from liver transported to adipose tissue?

Answer 13

Transported in blood plasma by VLDL proteins

Taken up by adipose where TGLs are digested by lipoprotein lipase to form FAs and acyl CoA

Question 14

What happens to FAs in well fed state?

Answer 14

FAs are oxidized in liver to produce

Acetyl CoA

Biosynthetic products via acetyl CoA

Minimal amount of ketones and ATP (enough glucose to meet energy needs of body)

See figure

Question 15

What happens to FAs during starvation (no glucose intake)?

Answer 15

most of the fatty acids are oxidized to ketones and ATP in order to meet the energy demands of the body, and to supply the energy needed for gluconeogenesis.

Question 16

Metabolism of Glucose, proteins and TGL in well fed state

Answer 16

See figure

Question 17

Metabolism in intestine during well fed state (mixed meal)

Answer 17

1) Carbohydrates are digested to glucose that is easily transported in the plasma to the liver
2) Lipids are transported as chylomicrons in the blood where they are digested by extrahepatic lipases into free fatty acids;
3) Proteins are digested by peptidases into free amino acids, and taken up by the liver

Question 18

Metabolism in blood plasma during well fed state (mixed meal)

Answer 18

4) Synthesis and secretion of insulin is stimulated.

It enhances the metabolism of glucose, amino acids, and triglycerides.

It diverts excess glucose into glycogen, fatty acids into triglycerides, and amino acids into proteins.

In contrast, the level of glucagon is low and has the opposite effects to insulin, where it acts exclusively on the liver to convert glycogen to glucose to maintain the plasma glucose level.

Question 19

Metabolism in blood plasma during well fed state (mixed meal)

Answer 19

4) Synthesis and secretion of insulin is stimulated.

It enhances the metabolism of glucose, amino acids, and triglycerides.

It diverts excess glucose into glycogen, fatty acids into triglycerides, and amino acids into proteins.

In contrast, the level of glucagon is low and has the opposite effects to insulin, where it acts exclusively on the liver to convert glycogen to glucose to maintain the plasma glucose level.

(10) Glucose in the blood plasma can be taken up by skeletal muscles and adipose tissues
(12) Chylomicrons and VDLP are converted by lipoprotein lipases into fatty acids (FA) and glycerol, which are taken up by adipose tissues

Question 20

Metabolism in liver plasma during well fed state (mixed meal)

Answer 20

(5) Most of the glucose is converted to glycogen, and the rest enters the glycolytic pathway.
(6) Some of the glucose in the glycolytic pathway is metabolized to produce ATP/Energy.
(7) Most of the glucose in the glycolytic pathway is converted to fatty acids and triglycerides. The triglycerides are released as very low density lipoproteins (VDLP) into the plasma

Question 21

Metabolism in brain plasma during well fed state (mixed meal)

Answer 21

(8) Glucose is metabolized in the glycolytic and TCA cycle mainly to produce ATP/energy

Question 22

Metabolism in RBC plasma during well fed state (mixed meal)

Answer 22

(9) Glucose is metabolized only via the glycolytic pathway to produce ATP/energy, pyruvate, and lactic acid.

Pyruvate and lactic acid are released into the plasma.

Question 23

Metabolism in Adipose tissue during well fed state (mixed meal)

Answer 23

(13) Glucose is converted to triglycerides, and FA and glycerol also combine to form triglycerides.

Question 24

Metabolism in tissue during well fed state (mixed meal)

Answer 24

(14) Amino acids are taken up to be converted to proteins, hormones, other important biomolecules, and ATP/energy via the TCA cycle.

Question 25

Interrelationship between glucose, lipid, and amino acid metabolism during the basal state of glucose homeostasis (12 hours after eating): Fasting State

Answer 25

See figure

Question 26

What is role of liver during fasting state?

Answer 26

Liver must feed glucose dependent tissues (brain and RBC)

Question 27

How does the liver supply glucose to brain and RBC during fasting?

Answer 27

Glycogenolysis (lasts 12 hours)

Gluconeogenesis (from amino acids, lactate which comes from RBC, and glycerol which comes from breakdown of TGL)

Also proceeds ketones from FAs

Question 28

What tissues use ketones?

Answer 28

Brain mainly (cannot oxidize FAs)

Other tissues (most tissues will oxidize FAs)

NOT RBC

Question 29

What do most tissues rely on during starvation?

Answer 29

Oxidation of fatty acids

EXCEPT BRAIN AND RBC

Question 30

What does brain rely on during starvation

Answer 30

Mainly ketones

Question 31

Interrelationship between the metabolism of glucose, fatty acids, and amino acids (5 days since the last meal): Starvation State

Answer 31

See figure

Question 32

What do RBC rely on during starvation?

Answer 32

Glucose exclusively

Question 33

Metabolic changes in different organs during starvation

Answer 33

See table

Question 34

Inter-organ Transfer of Metabolites after a Mixed Meal

Answer 34

See figure

Question 35

Inter-organ Transfer of Metabolites 12 hours after a Mixed Meal (B): postabsorptive state

Answer 35

See figure

Question 36

organ Transfer of Metabolites during Prolonged Fasting (C): starvation

Answer 36

See figure

Question 37

Deposition of metabolites after protein meal

Answer 37

See figure

Question 38

Deposition of metabolites after fat meal

Answer 38

See figure