Lecture 8: Integration of metabolism Flashcards
How does pyruvate serve as an intermediate?
links the metabolism of carbohydrates, lipids, and proteins.
What can pyruvate be converted into?
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
What metabolic pathways does the TCA cycle link?
Carbohydrates, lipids, and amino acids
What is produced in the TCA cycle?
Acetyl CoA
Reduced coenzymes
GTP
ATP (oxidative phosphorylation)
What major metabolic precursors can form acetyl CoA?
Pyruvate (from carbohydrates)
Fatty acids (from lipids)
Amino acids (from proteins)
What can acetyl CoA be converted into?
Lipids (via fatty acids)
Ketone bodies
Proteins (via amino acids)
Central molecule in the TCA cycle
See figure
What can citrate from TCA cycle be used for?
FA synthesis
What can oxaloacetate from TCA cycle be used for?
converted to aspartate and used to produce amino acids and nucleic acids
used within the urea cycle
synthesize glucose via gluconeogenesis.
What can alpha ketoglutarate from TCA cycle be used for?
transamination reactions by accepting the amino group to synthesize glutamate.
What can succinylcholine CoA from TCA cycle be used for?
synthesize haem
Conversion of glucose to FAs and TGLs
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
Conversion of glucose to FAs and TGLs
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
How are TGLs from liver transported to adipose tissue?
Transported in blood plasma by VLDL proteins
Taken up by adipose where TGLs are digested by lipoprotein lipase to form FAs and acyl CoA
What happens to FAs in well fed state?
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
What happens to FAs during starvation (no glucose intake)?
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.
Metabolism of Glucose, proteins and TGL in well fed state
See figure
Metabolism in intestine during well fed state (mixed meal)
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
Metabolism in blood plasma during well fed state (mixed meal)
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.
Metabolism in blood plasma during well fed state (mixed meal)
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
Metabolism in liver plasma during well fed state (mixed meal)
(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
Metabolism in brain plasma during well fed state (mixed meal)
(8) Glucose is metabolized in the glycolytic and TCA cycle mainly to produce ATP/energy
Metabolism in RBC plasma during well fed state (mixed meal)
(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.
Metabolism in Adipose tissue during well fed state (mixed meal)
(13) Glucose is converted to triglycerides, and FA and glycerol also combine to form triglycerides.
Metabolism in tissue during well fed state (mixed meal)
(14) Amino acids are taken up to be converted to proteins, hormones, other important biomolecules, and ATP/energy via the TCA cycle.
Interrelationship between glucose, lipid, and amino acid metabolism during the basal state of glucose homeostasis (12 hours after eating): Fasting State
See figure
What is role of liver during fasting state?
Liver must feed glucose dependent tissues (brain and RBC)
How does the liver supply glucose to brain and RBC during fasting?
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
What tissues use ketones?
Brain mainly (cannot oxidize FAs)
Other tissues (most tissues will oxidize FAs)
NOT RBC
What do most tissues rely on during starvation?
Oxidation of fatty acids
EXCEPT BRAIN AND RBC
What does brain rely on during starvation
Mainly ketones
Interrelationship between the metabolism of glucose, fatty acids, and amino acids (5 days since the last meal): Starvation State
See figure
What do RBC rely on during starvation?
Glucose exclusively
Metabolic changes in different organs during starvation
See table
Inter-organ Transfer of Metabolites after a Mixed Meal
See figure
Inter-organ Transfer of Metabolites 12 hours after a Mixed Meal (B): postabsorptive state
See figure
organ Transfer of Metabolites during Prolonged Fasting (C): starvation
See figure
Deposition of metabolites after protein meal
See figure
Deposition of metabolites after fat meal
See figure
