Nutrient Catabolism

BHCS1003 - CA05

Key Concepts

Catabolic Pathways: Energy- yielding breakdown reactions

Amphibolic pathways: serves both catabolic and anabolic roles

Oxidative phosphorylation: ATP generation usinf electrons from NADH and FADH2

Cellular Respiration

• Nutrient Oxidation → NADH/ FADH2

• Electrons donated to the electron transport chain

• Oxygen is the final electron acceptor → H2O

• Proton gradient drives ATP synthesis

Carbohydrate Catabolism - Glucose Catabolism

Gluocose is broken down via glycolysis to pyruvate, producing ATP and NADH

Key glycolytic itermediates:

• Glucose-6-phosphate (G6P)

• Fructose-6-phosphate (F6P)

• Glyceraldehyde-3-phophate (G3P)

• Pyruvate

Pyruvate is further oxidised via the TCA cycle and the OXPHOS

Fructose Metabolism

General features:

• Metabolised more rapidly than glucose

• Uptake is Insulin- independent

• Metabolic fate depends on nutritional state and organ type

In muscle:

• single step conversion to a glycolytic intermediate

In liver:

Requires multiple enzymatic steps

Disorders:

• Fructokinase deficiency → benign, fructose accumulates in blood and urine

• Hereditary Fructose intolerance (Aldolase B Deficiency) → severe liver damage if untreated

Galactose Metabolism

Occurs via Leloir Pathway → converted to glucose-6-phosphate

Disorder → Galactosemia (defect occurs in step 2)

Fatty acid Catabolism

Faty acids are a major energy source and are catabolised bia mitochondrial B-oxidation.

Main stages:

1) activation to fatty acyl-CoA

2) Transport into mitochondria

3) B-oxidation

4) Acetyl-CoA oxidation in the TCA cycle

Fatty Acid Activation

Key points:

• Catalysed by acyl-CoA synthetase

• Driven by pyrophosphate Hydrolysis

• Enzymes show chain length specificity

Transport into Mitochodria

Requires Carnitine shuttle

Catalysed by Carnitine Palmitoyltansferase (CPT)

2 cpt isozymes involved

Mitochondrial B-Oxidation

• Oxidation occurs at the beta-carbon of the fatty acyl-CoA

• each cycle yields:

→ Acetyl-CoA

→ NADH

→FADH2

→ fatty acyl-CoA shortened by 2 carbons

• processes repeats until fatty aid is fully degraded

Special Mechanisms exist for:

• very long chain fatty acids

• unsaturated fatty acids

Reoxidation of NADH and FADH2

NADH feeds electrons into complex I

FADH2 donates electrons via:

electron-tranfers flavoprotein (ETF)

Complex II (succinate dehydrogenase)

electrons pass through Q, complex III, cytochrome c and complev IV

OXGYEN IS REDUEED TO WATER

Amino Acid Catabolism

• Amino acids come from dietary protein or muscle breakdown

• Important during fasting or disease states

Associated conditions:

• sarcopenia: age-related muscle loss (ageing, CKD, liver disease)

• Cachexia: severe muscle wasting

Deamination and Nitrogen Disposal

• Amino acid catabolism involves deamination

• produces ammonia (NH3) which is toxic

Urea Cycle (krebs-Henseleit cycle)

• Converts toxic ammonia into urea for excretion

• Functionally linked to the TCA Cycle

• Discovered by Hans Krebs

Glucogenic vs Ketogenic Amino Acids

Glucogenic Amino Acids: form glucose via TCA Cycle intermediates

Ketogenic amino acids: form acetyl-CoA or ketone bodies

Some amino acids are both

Metabolic Convergence

Carbohydrates→ glycolysis → TCA cycle

Fatty acids→ acetyl-CoA → TCA cycle

Amino Acids → TCA cycle intermediates

All major nutrients converge on the TCA cycle and oxidative phosphorylation to generate ATP