Fatty acid synthesis

Nitrogen metabolism goal

Convert toxic ammonia into urea for safe excretion

Urea cycle location

Liver

Sources of amino acids

Diet, protein turnover, de novo synthesis

Transamination

Transfer of amino group to α-ketoglutarate to form glutamate

Transamination cofactor

Pyridoxal phosphate (PLP, vitamin B6)

Central nitrogen carrier

Glutamate

Oxidative deamination

Removal of amino group from glutamate to release ammonia

Oxidative deamination enzyme

Glutamate dehydrogenase

Ammonia toxicity

Causes neurological damage and brain swelling

Final nitrogen excretion product

Urea

Fatty acid functions

Energy storage, membrane structure, signalling, insulation

Storage form of fatty acids

Triacylglycerols (triglycerides)

Triglyceride structure

Glycerol + 3 fatty acids

Triglyceride storage location

Adipose tissue (adipocytes)

Why triglycerides are energy dense

Highly reduced molecules

Fatty acid synthesis location

Cytosol

Rate-limiting step of FA synthesis

Formation of malonyl-CoA

Key enzyme in FA synthesis

Acetyl-CoA carboxylase (ACC)

ACC reaction

Acetyl-CoA + CO₂ + ATP → Malonyl-CoA

ACC activators

Insulin, citrate

ACC inhibitors

Glucagon, epinephrine, palmitoyl-CoA

Effect of phosphorylation on ACC

Inactivates enzyme

Effect of dephosphorylation on ACC

Activates enzyme

Role of malonyl-CoA

Substrate for FA synthesis and inhibitor of CPT-I

Fatty acid synthase (FAS)

Multifunctional enzyme complex that synthesises fatty acids

Main product of FAS

Palmitate (C16)

FAS primer

Acetyl-CoA

FAS carbon donor

Malonyl-CoA

FAS reducing agent

NADPH

FAS cycle steps

Condensation, reduction, dehydration, reduction

Number of cycles to form palmitate

7

Citrate shuttle function

Transports acetyl-CoA from mitochondria to cytosol

Citrate role in metabolism

Signals energy abundance and activates ACC

Fatty acid elongation location

Endoplasmic reticulum and mitochondria

Function of elongation

Adds 2-carbon units to fatty acids

Fatty acid desaturation location

Endoplasmic reticulum

Function of desaturation

Introduces double bonds into fatty acids

Limitation in humans

Cannot introduce double bonds beyond carbon 9

Essential fatty acids

Linoleic acid and linolenic acid

Fatty acid oxidation location

Mitochondrial matrix

Products of β-oxidation

Acetyl-CoA, NADH, FADH₂

Fate of acetyl-CoA

Enters TCA cycle or forms ketone bodies

Ketone bodies definition

Water-soluble fuels derived from fatty acids

Ketone body synthesis location

Liver mitochondria

Types of ketone bodies

Acetoacetate, β-hydroxybutyrate, acetone

Conditions for ketone production

Fasting, starvation, low carbohydrate intake, uncontrolled diabetes

Cause of ketone formation

Excess acetyl-CoA and low oxaloacetate

Rate-limiting enzyme of ketogenesis

HMG-CoA synthase

Ketone body utilisation location

Extrahepatic tissues (muscle, brain, heart)

Ketolysis definition

Conversion of ketone bodies into acetyl-CoA

Key enzyme in ketolysis

Thiophorase

Why liver cannot use ketones

Lacks thiophorase

Fed state metabolism

Fatty acid synthesis and energy storage

Fasting state metabolism

Fatty acid oxidation and ketone body production

Hormonal control of metabolism

Insulin promotes storage, glucagon promotes breakdown