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Metabolic Pathways for Lipids.

Ketogenesis and Ketone Bodies.Fatty Acid Synthesis.

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Ketogenesis and Ketone Bodies

In ketogenesis: Body fat breaks

down to meet energy needs.

Keto compounds called ketone bodies form.

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Ketogenesis and Ketone Bodies

In ketogenesis: Large amounts of acetyl CoA accumulate. Two acetyl CoA molecules combine to form

acetoacetyl CoA. Acetoacetyl CoA hydrolyzes to acetoacetate, a

ketone body. Acetoacetate reduces to -hydroxybutyrate or

loses CO2 to form acetone, both ketone bodies.

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Reactions of Ketogenesis

Ketone bodies

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Ketosis

Ketosis occurs: In diabetes, diets high

in fat, and starvation. As ketone bodies

accumulate. When acidic ketone

bodies lowers blood pH below 7.4 (acidosis).

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Ketone Bodies and Diabetes The blood glucose is elevated

within 30 min following a meal containing carbohydrates

The elevated level of glucose stimulates the secretion of insulin, which increases the flow of glucose into muscle and adipose tissue for synthesis of glycogen (+ stimulates glycolysis)

As blood glucose levels drop, the secretion of glucagon increases, which stimulates the breakdown of glycogen in the liver to yield glucose

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Ketone Bodies and DiabetesIn diabetes: Insulin does not function properly. Glucose levels in muscle, liver, and

adipose tissue are insufficient for energy needs.

As a result, liver cells synthesize glucose from non-carbohydrate sources (gluconeogenesis) and fats are broken down to acetyl CoA.

The level of acetyl CoA is elevated. Excess acetyl CoA undergoes

ketogenesis. Ketogenesis produces ketone bodies. Ketone bodies accumulate in the blood.

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Lipogenesis: Fatty Acid Synthesis

Lipogenesis: Is the synthesis of fatty acids from acetyl CoA. Occurs in the cytosol. Uses reduced coenzyme NADPH (NADH with a

phosphate group). Requires an acyl carrier protein (ACP).

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Malonyl CoA

In lipogenesis, acetyl CoA combines with bicarbonate to form malonyl CoA. ATP hydrolysis provides energy. O

|| CH3—C—S—CoA + HCO3

- + ATP Acetyl CoA

O O || ||

-O—C—CH2—C—S—ACP + ADP + Pi

Malonyl CoA

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Formation of Acetyl and Malonyl ACP

Acetyl CoA and malonyl CoA combine with acyl carrier protein (ACP) to form acetyl-ACP and malonyl-ACP:

O ||CH3—C—S—ACP Acetyl-ACP

O O || ||

-O—C—CH2—C—S—ACPMalonyl-ACP

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Condensation and Reduction

In reactions 1 and 2 of fatty acid synthesis:

Condensation by a synthase combines acetyl-ACP with malonyl-ACP to form acetoacetyl-ACP (4C) and CO2 (reaction 1).

Reduction converts a ketone to an alcohol using NADPH (reaction 2).

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Dehydration and Reduction

In reactions 3 and 4 of fatty acid synthesis:

Dehydration forms a trans double bond (reaction 3).

Reduction converts the double bond to a single bond using NADPH (Reaction 4).

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Lipogenesis Cycle Repeats

Fatty acid synthesis continues:

Malonyl-ACP combines with the four-carbon butyryl-ACP to form a six-carbon-ACP.

The carbon chain lengthens by two carbons each cycle.

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Lipogenesis Cycle Completed

Fatty acid synthesis is completed when palmitoyl ACP reacts with water to give palmitate (C16)

and free ACP.

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Summary of Lipogenesis

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Fatty Acid Formation

Shorter fatty acids undergo fewer cycles. Longer fatty acids are produced from palmitate

using special enzymes. Unsaturated cis bonds are incorporated into a

10-carbon fatty acid that is elongated further. When blood glucose is high, insulin stimulates

glycolysis and pyruvate oxidation to obtain acetyl CoA to form fatty acids.

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Comparing Oxidation and Fatty Acid Synthesis