Lecture 21: Gluconeogenesis Flashcards by Brooke Thornburg

Role of Liver as energy provider

-maintain blood glucose by glycogen breakdown and gluconeogenesis
-produce ketone bodies in ketogenesis

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*Carbon sources of gluconeogenesis

-lactate
-amino acids
-glycerol
-fructose

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Energy source of gluconeogenesis

ATP from FATTY acid OXIDATION

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*Rate-limiting step of gluconeogenesis

-step catalyzed by pep carboxykinase

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Gluconeogenesis

-liver producing glucose
-many enzymes reused except irreversible steps

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Gluconeogenesis reaction

lactate to pyruvate to oxaloacetate (occurs in TCA cycle) to phosphoenolpyruvate

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Oxaloacetate in gluconeogensis

-comes from TCA cycle
-transported from mitochondria via aspartate/malate shuttle

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*Futile cycle regulation glycolysis vs gluconeogenesis

-G6Pase expressed ONLY in liver
-6-phosphofructokinase and pyruvate kinase regulated ALLOSTERICALLY

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Glucose to pyruvate ATP

-YIELDs 7 ATP

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Pyruvate to glucose ATP

-NEEDS 11 ATP

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Glucokinase

-replaces hexokinase in the liver
-uses glucose only when there is a LOT
-futile system with G6Pase keeps blood sugar up

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Activation of Gluconeogenesis

-inhibition of glycolysis
-fatty acid oxidation
-increase in citrate

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Inhibition of glycolysis

ATP inhbits 6phosphofructokinase and pyruvate kinase

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Fatty Acid oxidation

-supplies ATP for gluconeogenesis
-increase acetyl CoA that INactivates pyruvate DEHYDrogenase and ACTIVATES pyruvate CARBoxylase

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Increase in citrate

-caused by increase in oxaloacetate and acetyl CoA
-negative allosteric regulator of 6phosphofuctokinase

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CHART SLIDE 9

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Alcohol and gluconeogenesis

-oxidation of ethanol by liver depletes NAD+
-excess NADH converts pyruvate to lactate
-gluconeogenesis by liver is suppressed

Problems of alcohol

-hypoglycemia
-lactic acidosis
-problem more severe when glycogen storage in liver is depleted (malnutrition/exercise)

Pentose Phosphate Pathway

-produces NADPH
-produces ribose-5-phosphate used for DNA synthesis

Pentose Pathway rate-limiting AND commintment step

-first step

G6P fate

-glycolysis
-glycogen synthesis
-PPP
-glucose production in liver

NADH sources

-glycolysis
-TCA
-fatty acid oxidation

NADH uses

-generation of ATP by oxidative phosphorylation

NADPH sources

-PPP

NADPH uses

-anabolic reactions

Ketone bodies

-water soluble products of lipid oxidation (acetyl CoA) -produced by liver during fasting -reduces need for gluconeogenesis -reduces protein wasting -used by brain and skeletal muscles as fuel

Ketone body synthesis

-mitochondria -HMG-CoA synthase expressed at high levels during fasting 1. 2 acetyl CoA (C2) --> acetoacetyl CoA 2. Acetoacetyl CoA + acetyl CoA --HMGsynthase--> HMG-CoA (C6)

ratio of acetoacetic acid to B-hydroxybutyric acid

-dependent on ration of NAD+/NADH in liver mitochondria

ketoacidosis

-high concentration of ketone bodies -leads to spontaneous production of acetone from acetoacetic acid

Using ketone bodies

-converted to acetyl CoA in mitochondria outside liver -reducing equivalent in B-hydroxybutyric acid harvested as NADH -acetyl CoA used as fuel in TCA cycle

B-hydroxybutyric acid to acetyl-CoA

-to acetoacetic acid first -then to acetoacetyl CoA = 2 acetyl CoA

Energy sources for physical activities

-fatty acid and ketone bodies are preferred to glucose when O2 is sufficient

Fatty Acid oxidation increases Citrate

-suppresses glycolysis -similar to switching between glycolysis and gluconeogenesis

Slide 18

come on u got this king

Ketoacidosis

-mostly in type I diabetics -low insulin promots lipolysis in adipose tissue -production of lots of ketone bodies LOWERS blood pH -medical emergency

When the blood glucose levels are low, which of the following reactions is suppressed in the liver? -Conversion of fatty acids to acetyl CoA -Conversion of pyruvate to acetyl CoA -Conversion of pyruvate to oxaloacetate -Conversion of oxaloacetate to phosphoenolpyruvate -Conversion of lactate to pyruvate

Conversion of pyruvate to acetyl CoA