NS 315Unit 4: Carbohydrate Metabolism

Jeanette Andrade MS,RD,LDN,CDE

Kaplan University

Objectives

We want to learn about: Glycolysis and ATP formation

Understand Gluconeogenesis, when, where and how

Krebs Cycle and Electron Transport Chain

Definitions

Glycolysis: central pathway for the catabolism of carbohydrates; occurs in most organs

Gluconeogenesis: Biosynthesis of new glucose; occurs mainly in liver

Krebs cycle- series of enzymatic reactions in aerobic organisms involving oxidative metabolism of acetyl units and producing high-energy phosphate compounds, which serve as the main source of cellular energy

Electron Transport Chain (ETC)- Composed of mitochondrial enzymes that transfers electrons from one transport to another, resulting in the driving force for the formation of ATP

Oxidative phosphorylation- Process occurring in the cell, which produce energy and synthesizes ATP

Definitions

Pyruvate: final 3 carbon molecule of glycolysis, involved in the Krebs cycle which facilitates energy production

Adenosine diphosphate/Adenosine triphosphate: energy storing molecule used by an organism on a daily basis

NAD/NADPH: Reducing agent in several anabolic reactions such as lipid and nucleic acid

FAD/FADH: Reducing agent in several anabolic reactions such as lipid

Aerobic: in the presence of oxygen

Anaerobic: no presence of oxygen

Glycolysis Animation

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter25/animation__how_glycolysis_works.html

Fates of PyruvateUnder aerobic conditions

Under anaerobic conditions

In most aerobic organisms, pyruvate continues in the formation of Acetyl CoA and NADH that follows into the Krebs cycle and

Under anaerobic conditions, such as during exercise or in red blood cells (no mitochondria), pyruvate is reduced to lactate by lactate dehydrogenase producing NAD for glycolysis

Pathways during Glycolysis

Aerobic- with oxygen

The main energy releasing pathway in most human cells

Continues in the mitochondrion where oxygen serves as the final electron acceptor

1 glucose + 6 oxygen 6 carbon dioxide +6 water

36 or 38 ATPs are produced (total after all cycles: glycolysis, krebs and ETC)

Anaerobic- without oxygen

Fermentation pathway and anaerobic electron transport- many bacteria and humans, when oxygen is limited, use this pathway

Ends in the cytoplasm where other substances besides oxygen is the final electron receptor

Only 2 ATP are produced

Gluconeogenesis

During starvation (not eating for 16 hours plus), the brain can use ketone bodies for energy by converting to Acetyl CoA, usually gluconeogenesis creates glucose when glycogen stores are depleted

Synthesis of glucose from 3-4 carbon precursors is a reversal of glycolysis

2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi

Gluconeogenesis

3 reactions in glycolysis are essentially irreversible, thus they are bypassed in gluconeogenesis: Hexokinase (1) Phosphofructokinase (3) Pyruvate Kinase (10)

Share 7 of the 10 steps in glycolysis

Fed state

Cytoplasm

All cells

Fasting state

Cytoplasm

Liver mostly, but also kidney

Glycolysis vs Gluconeogenesis

Activation of Pyruvate

Before the Kreb’s cycle begins, pyruvate must be activated into acetyl CoA

Pyruvate dehydrogenase complex (PDHC) is an enzyme that catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA

PDHC is a multi-enzyme comprising of 5 coenzymes- which include many vitamins such as thiamin (thiamin pyrophosphate), riboflavin (FAD), and niacin (NAD)

Krebs Cycle

Also known as the citric acid cycle or tricarboxylic acid (TCA) cycle

Under aerobic conditions pyruvate enters the mitochondria MATRIX and is oxidized to Acetyl CoA which enters the Krebs cycle

Krebs cycle can occur after glycolysis, after Beta oxidation or protein degradation to provide energy for cellular respiration

Equation for Krebs cycle with the beginning products and the ending. 8 steps involved

2 pyruvate + 2 GDP + 2 H3PO4 + 4 H2O + 2 FAD + 8 NAD+ ----> 6 CO2 + 2 GTP + 2 FADH2 + 8 NADH

Krebs Cycle

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter25/animation__how_the_krebs_cycle_works__quiz_1_.html

Summary TCA

Occurs in the mitochondrial matrix

Uses acetyl CoA to produce: 3 NADH, 1 FADH, 1 GTP, 2CO2

Produce intermediates for biosynthetic pathways such as aminoacid synthesis, gluconeogenesis, pyrimidine synthesis, phorphyrin synthesis, fatty acid synthesis, isoprenoid synthesis.

Electron Transport Chain (ETC)

Final pathway by which electrons generated from oxidation of carbs, protein and fatty acids, are ultimately transferred to O2 to produce H20

Located in the inner mitochondrial membrane Electrons travel down the chain, pumping protons into the

intermembrane space creating the driving force to produce ATP in a process called oxidative phosphorylation

There are 4 complexes that comprise the ETC

Electron Transport Chain

http://vcell.ndsu.edu/animations/etc/movie.htm

Summary ETC

Reduced electron carriers NADH & FADH2 reduce O2 to H2O via the ETC. The energy released creates a proton gradient across the inner mitochondrial membrane. The protons flow down this concentration gradient back across the inner mitochondrial membrane through the ATP Synthase. The driven force makes this enzyme rotate and this conformation generates enough energy to make ATP.

Oxidation of NADH to NAD+ pumps 3 protons which charges the electrochemical gradient with enough potential to generate 3 ATPs.

Oxidation of FADH2 to FAD+ pumps 2 protons which charges the electrochemical gradient with enough potential to generate 2 ATPs.