Stages of Catabolism

Info from ch 14. Know where metabolic pathways take place Stages of Catabolism

Intro to Pathways • Identify the functions • Identify the overall starting materials and

products • Compartmentation • Aerobic or anaerobic • Catabolic or Anabolic

Glycolysis (Embden-Meyerhof-Parnas pathway)

• Glycolytic endpoints – depending on which cell and conditions, glucose metabolism results in the production of ethanol, lactate and CO2, H2O via pyruvate

• This is the predominant fate of glucose in mammalian cells

• Limited potential energy w/o O2 . Captured as ATP • Pathway is found in all cells of the body • This is primarily a cytosolic pathway

• Net reaction: Glucose + 2 ADP +2 Pi + 2 NAD+ <-> 2 Pyruvate + 2 ATP + 2

NADH

Glycolysis

Predominant fate of glucose in mammalian cells;

ATP production under anaerobic conditions. Cytosolic

Pathway is found in all cells of the body.

In red blood cells, this is the ATP producing pathway since they have no mitochondria.

• Gluconeogenesis – Generation of glucose from noncarbohydrate precursors – The principle noncarbohydrate precursors of glucose

are lactate, pyruvate, citric acid cycle intermediates and most of the standard amino acids.

– Main function is to make glucose to release into circulation to maintain proper blood glucose levels.

– Triggered by low blood glucose levels –

• Overall reaction (example)

• 2 pyruvate + 4 ATP + 2 GTP + 2 NADH + 6 H2O  Glucose + 4 ADP + 2 GDP + 6 Pi + 2 NAD+ + 2 H+

Gluconeogenesis

Starts with pyruvate

Synthesis of glucose from noncarbohydrate precursors.

Takes place in the liver and kidney only. The first reaction is mitochondrial and the rest are cytosolic. Stimulated when blood glucose levels are low. This triggers glucagon release which stimulates this pathway.

Pentose Phosphate Pathway • 3 glucose 6 P + 6 NADP+ + 3 H2O 

6 NADPH + 6 H+ + 3 CO2 + 3 Ribulose 5 P.

NADPH is the biological reducing agent required for biosynthetic processes. Also required for the cells to deal with oxidative stress.

• Cytosolic • Many tissues (especially liver, mammary

gland, adipose tissue and adrenal cortex)

Glycogenesis (glycogen synthesis) and glycogenolysis (glycogen breakdown)

• Glycogenesis – Addition of glucose units to pre-existing

glycogen molecules, using UDP-glucose as activated glucose donor

– Triggered by high blood glucose levels

Glycogenesis (glycogen synthesis) and glycogenolysis (glycogen breakdown)

• Glycogenolysis – Release of glucose as glucose-phosphate from

stored glycogen molecules – Triggered by low blood glucose levels

Mitochondria – pathways that require O2

• Pyruvate Dehydrogenase complex

• Citric acid cycle (TCA, tricarboxylic acid cycle)

• Electron transport coupled to oxidative phosphorylation

• Overall aerobic catabolism Glucose + 6 O2  6 CO2 + 6 H2O

• Fatty acid beta oxidation

Pyruvate Dehydrogenase • The aerobic utilization of pyruvate

produced in glycolysis. • Overall of the five reactions • Pyruvate + CoA + NAD+ 

acetyl CoA + CO2 + NADH

O2 not directly involved, but required for NADH to be re-oxidized in electron transport coupled to oxidative phosphorylation.

Fatty Acid Beta Oxiation • Catabolic pathway in which fatty acids

are oxidatively degraded to yield acetyl- CoA, NADH and FADH2

• Takes place in the mitochondrial matrix. • Overall reaction for degradation of a 16 C

saturated fatty acyl CoA • Palmitic

Citric Acid cycle (TCA) • Takes place in mitochondria in the matrix

Oxidation of Acetyl CoA (another cross road metabolite) to release CO2 and reduced coenzymes.

– Sources of acetyl CoA – From pyruvate dehydrogenase comples (from glucose via

glycolysis) • ß oxidation of fatty acids – releases acetyl CoA • selected amino acids – deaminated to release acetyl CoA

• Utilizes biological oxidizing agents NAD+ and FAD, producing NADH and FADH2.

• An aerobic pathway because O2 is necessary to reoxidize these reduced coenzymes.

• Function is to oxidize products of stage 2 catabolism to release carbons as CO2 and produce ATP and reduced coenzymes which will result in ATP production in electron transport coupled to oxidative phosphorylation

• Also has some biosynthetic purposes Intermediates of pathway used as biosynthetic precursors.

Overall Reaction of one round of TCA: 3 NAD+ + FAD + GDP + Pi + acetyl-CoA 

3 NADH + FADH2 + GTP + CoA + 2 CO2

AGAIN – YOU DO NOT NEED TO MEMORIZE ANY OF THESE INDIVIDUAL STEPS at this time.

Cyclic – Oxaloacetate –

– only a small amount is needed – catalytic role

– Anapleurotic –

– “filling up” cycle can be used as entry and exit for production of other essential metabolites

Electron Transport Coupled to Oxidative Phosphorylation

• Multiple steps used to reoxidize NADH and FADH2 to NAD+ and FAD

• O2 is the final electron acceptor (strongest oxidizing agent) of the chain.

• Free energy produced from a proton gradient generated across the mitochondrial inner membrane used to drive the synthesis of ATP.

Morphology of Inner Mitochondrial Membrane and Electron Transport and Oxidative Phosphorylation

NADH

• Overall reaction of Electron Transport – NADH + ½ O2 + H+  H2O + NAD+

• Overall reaction of Oxidative Phosphorylation (synthesis of ATP coupled to electron transport). – ADP + Pi  ATP + H2O catalyzed by ATP

Synthase complex. • Function(s): Regenerate oxidized forms of

redox coenzymes • Produce majority of ATP from the

catabolism of our fuels under aerobic conditions

• Overall reaction of Electron Transport – NADH + ½ O2 + H+  H2O + NAD+

• Overall reaction of Oxidative Phosphorylation (synthesis of ATP coupled to electron transport). – ADP + Pi  ATP + H2O catalyzed by ATP Synthase

complex. • Function(s): Regenerate oxidized forms of redox

coenzymes • Produce majority of ATP from the catabolism of

our fuels under aerobic conditions. • 2.5 ATP/NADH and 1.5 ATP/FADH2

ATP Yield from Catabolism of Glucose

• How many ATP per glucose catabolized under anaerobic conditions? – Look at glycolysis. Net of 2 ATP

ATP Yield from Catabolism of Glucose

• How many ATP per glucose catabolized under aerobic conditions? – Count all of the ATP (and GTP), NADH and FADH2

produced starting with glucose completely catabolized to CO2 and H2O

– 2 ATP + 2 NADH from glycolysis (7 ATP) – 2 NADH from PDH (5 ATP) – 6 NADH from 2 rounds of TCA (15 ATP) – 2 GTP from 2 rounds of TCA (2 ATP) – 2 FADH2 from 2 rounds of TCA (3 ATP) – Net of 32 ATP

Learning Goals. After reviewing these notes you will be able to:

• Identify the pathways that are stage 1, 2 and 3 catabolism.

• Recognize whether a pathway is catabolic or anabolic based on the description.

• List examples of catabolic and anabolic pathways.

• Discuss the major metabolic functions of cytosol, mitochondria, smooth and rough endoplasmic reticulum, golgi apparatus,

Learning Goals: you should be able to state the function, give overall reactions (major substrates and

products), compartmentation of the following pathways:

• Glycolysis • Gluconeogenesis • Pentose phosphate pathway • Glycogenesis • Glycogenolysis • Fatty acid oxidation • Citric Acid cycle (TCA) • Electron transport • Oxidative phosphorylation