Gluconeogenesis + Reading 3

BIOC13

Main transformation of gluconeogenesis

2 pyruvate to 1 glucose

Sites for complete gluconeogenesis

Liver, kidney

Net reaction

2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 2 H+ + 6 H2O → glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+

Making glucose from amino acids

Carbon skeletons can form gluconeogenic intermediates

Making glucose from glycerol

Can be converted to DHAP

Making glucose from lactate

Lactate dehydrogenase catalyzes a reaction that forms pyruvate from lactate

Cori Cycle

Lactate produced by muscles enters blood, producing glucose when taken from blood by liver, or converted to pyruvate for citric acid cycle and oxidative phosphorylation in other cells

Enzyme that bypasses hexokinase

G-6-Pase

Enzyme that bypasses PFK

F-1,6-BPase

Enzymes that bypass pyruvate kinase

Pyruvate carboxylase and PEP carboxylase

Intermediate in bypassing pyruvate kinase (by pyruvate carboxylase and PEP carboxylase)

oxaloacetate

Coenzyme required in formation of oxaloacetate

Biotin (vitamin B7)

Purpose of coenzyme in oxaloacetate formation

Carrier in CO₂ transfersT

Transportation of oxaloacetate from mitochondria to cytoplasm

Reduced to malate, carried by malate transported, then reoxidized to oxaloacetate in cytoplasm, catalyzed by malate dehydrogenase

Why does metabolism of PEP require ATP

Inorganic phosphate present

Last step of gluconeogenesis in tissues besides liver

G-6-P

Differential Gene expression

Gene duplications and alternative splicing

Competing allosteric regulators of PFK

ATP and AMP

Enzyme that increases AMP levels

Adenylate kinase: makes ATP and AMP from 2 ADP

High G-6-P indicates

Increase in glycolysis and regulation OR reduced gluconeogenesis

Insulin

Hormone released with high blood glucose levelsG

glucagon

Hormone released with low blood glucose levels

How does glucose trigger insulin from pancreatic b cells

Glucose metabolism produces ATP, closing a K⁺ channel and opening a Ca²⁺ channel, influx of Ca²⁺ stimulates release of insulin

Muscle and adipocyte response to insulin

increase GLUT4 to increase removal of glucose

Key control point between glycolysis and gluconeogenesis

F-6-P ↔ F-1,6-BP

Enzyme that synthesizes F-2,6-BP

PFK2

Enzyme that hydrolyzed F-2,6-BP

FBPase2

Bifunctional enzyme

Two enzymes located on the same polypeptide chain, like PFK2/FBPase2

Pathway that regulates PFK2/FBPase2

Glucagon signaling pathway phosphorylation

Enzyme active during low blood glucose

FBPase2

Enzyme active during high blood glucose

PFK2

Regulation of pyruvate kinase in cancer cells

PK in cancer cells has a lower baseline activity, PK can increase in activity if the cell requires more energy or if there is a buildup of serine or FBP