NS 315 Unit 4: Carbohydrate Metabolism Penni Davila Hicks, PhD, RD,LD Kaplan University

Objectives We want to learn about: Review carbohydrate digestion/absorption Glycolysis Gluconeogenesis Krebs Cycle Electron Transport Chain 2 2

Definitions 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 3

Definitions Pyruvate: final 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 4 4

Importance of Glucose Carbohydrates are broken down to simplest form Polysaccharides to monosaccharides or glucose Glucose is essential for our survival Especially for: Brain Central Nervous System Red Blood Cells

Glycogenesis Synthesis of glycogen from excess glucose that takes place in liver and muscle. Liver is the major site of glycogen synthesis and storage Liver plays an important role in maintaining blood glucose Muscle stores most of the glycogen in the body and used at time of physical exertion (no synthesis here) When blood glucose is high insulin stimulates glycogenesis Glycogen if vitally important in ensuring a reserve of instant energy Synthesis of a linear and branched glucose polymer (glycogen) from excess glucose in liver and muscle.

Glycogenolysis Breakdown of glycogen into glucose At times of energy demands Takes place in liver and muscle Regulated by glucagon Glucose from liver can be used to maintain blood glucose levels and to produce energy or ATP

Glycolysis The breakdown or oxidation of glucose to two pyruvate molecules that occurs in the cytosol. The metabolic fate of pyruvate is different under aerobic conditions and anaerobic conditions. Aerobic conditions – pyruvate enter the Krebs cycle to produce ATC Anaerobic conditions – pyruvate is converted to lactate

Fates of Pyruvate Under 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 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 10

Pathways during Glycolysis Anaerobic- without oxygen Aerobic - with oxygen available to the cells Pyruvate → mitochondria The main energy releasing pathway in most human cells 36 or 38 ATPs are produced (total after all cycles: glycolysis, krebs and ETC) Fermentation pathway and anaerobic electron transport- many bacteria and humans, when oxygen is limited, use this pathway Only 2 ATP are produced Pyruvate enters mitochondria for complete oxidation 11 11

Gluconeogenesis Synthesis of glucose from non-carbohydrate precursors, amino acids, lactate & glycerol, occurs in both the mitochondria and cytosol of the liver (and to some extent the kidney during starvation) Gluconeogenesis is a reversal of glycolysis 2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi 12 12

Gluconeogenesis During starvation (not eating for 16 hours or more), the brain can use ketone bodies from glycerol for energy by converting to Acetyl CoA Usually gluconeogenesis creates glucose when glycogen stores are depleted 2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi 13 13 13

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 14 14

Glycolysis vs Gluconeogenesis Fed state Glucose→Pyruvate Cytoplasm All cells Fasting state Cytoplasm Liver mostly, but also kidney Non-carb source → Glucose 15 15

Krebs Cycle Acetly Co A begins the 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 Acetly Co A begins the Krebs cycle

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Activation of Pyruvate First step activates pyruvate to acetyl CoA. Pyruvate Dehydrogenase Complex (PDHC) catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA PDHC is a multienzyme comprising of 5 coenzymes (some vitamins): thiamin pyrphosphate (thiamin), CoA, lipoic acid, FAD (riboflavine) and NAD (niacin)

PDHC

Summary TCA Occurs in the mitochondrial matrix Uses acetyl CoA to produce ATP NADH, FADH2, 2Co2 Produce intermediates for biosynthetic pathways such as amino acid synthesis, gluconeogenesis, pyrimidine synthesis, phorphyrin synthesis, fatty acid 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 We can make ATP from ATP

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.