Lecture 8: Carbon Metabolism

Cell Metabolism

• the sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others

• anabolism and catabolism dependent on ΔH values

Main Purposes of Cell Metabolism

• conversion of food to energy to run cellular processes

• conversion of food/fuel to building blocks for proteins, lipids, nucleic acids, and some carbohydrates

• elimination of nitrogenous wastes: ammonia via urea cycle

Carbon Metabolism

• mostly linked to energy metabolism, cellular respiration

• sugars

• lipids, especially free fatty acids and triglycerides

Carbon Metabolism in Human Body

• carbon fixation/assimilation in the plants and bacteria

  • photosynthesis (CO₂ incorporated into organic compounds (sugars)

    • light reaction

    • dark reaction: Calvin’s cycle

Carbon Metabolism: Nutrient Digestion

food sugars and lipids

Carbon Metabolism: Carbohydrate Metabolism

glucose cellular respiration, gluconeogenesis

Carbon Metabolism: Lipid Metabolism

free fatty acids, triglycerides, cholesterol, phospholipids

Biogeochemical Cycle

pathway where a chemical substance cycles (turns over or moves through) the biotic and abiotic compartments of Earth

Biotic Compartment

biosphere, everything living

Abiotic Compartments

atmosphere, hydrosphere, lithosphere, everything non-living

Energy Metabolism

• generating biochemical energy (ATP) from nutrients, mostly starting from glucose and TG, merging at acetyl Coenzyme A (CoA)

• providing ATP or NAD(P)H to convert endergonic reactions into overall exergonic reactions

Two Types of Energy Metabolism

aerobic, anaerobic

Aerobic Metabolism

• refers to cellular respiration

• converting sugras (via glucose) or TG molecules into ATP molecules

• O₂ dependent

Anaerobic Metabolism (Fermentation)

• less efficient than aerobic

• O₂ deficient

• functional hypoxia during vigorous exercise

• tumor growth, especially solid tumors

• providing energy for survival of anaerobic organisms/species: some bacteria, protozoans

Cell Metabolism Regulation

• achieves steady state/homeostasis of intermediate metabolites

• disruption of steady state/homeostasis leads to disease

Key Goals of Carbon Metabolism Regulation: ATP

• continuously provide ATP to maintain cellular respiration

• ATP continuously used by muscle and brain

  • primary: glucose cellular respiration

  • secondary: TG cellular respiration

Key Goals of Carbon Metabolism Regulation: Steady State

• ensure the blood (glucose) is always under steady state (normoglycemia)

  • other sugars and TG can be considered as glucose precursors

    • merging at acetyl CoA into respiration

Dysglycemia

hyperglycemia (in diabetes) or hypoglycemia

Energy Flow

• refers to energy metabolism

  • metabolic process of high energy ATP generation, which can be used by other energy demanding metabolic processes

Cellular Respiration: Aerobic Metabolism

• a set of metabolic reactions and processes that take place in the cells to convert biochemical energy from nutrients into ATP, and then release waste products

• oxygen dependent

• external nutrients can’t be directly incorporated into body

  • digestion (to release energy and intermediates) and assimilation

Cellular Respiration: Sugars via Glucose

• primary energy production process starting from glucose

• glucose, glycolysis, pyruvate, acetyl CoA, Krebs Cycle, NADH + QH₂, oxidative phosphorylation, ATP

• oxygen dependent

Cellular Respiration: TG

• lipolysis, backup energy production starting from TG

  • energy flow from TG into ATP

  • QH₂, merging into glucose cellular respiration process, ATP

  • oxygen dependent

Glycolysis Introduction

• one step of glucose cellular respiration

• most cells have the glycolytic pathway

• every intermediate serves as an intermediate in another pathway in most cells

  • metabolic crossroads

Glycolysis Key Purpose

forming ATP, NADH, (ETC of O.P.), and generating pyruvate (Krebs Cycle)

Glycolysis Overall Reaction

• catalysis by 10 enzymes in order

• overall reaction: converts 1 glucoses to 2 pyruvate

• ATP and NADH are mobile cofactors

Glycolysis Enzymes

hexokinase, phosphoglucose isomerase, phosphofructosekinase 1, aldolase, triose phosphate isomerase, glyceraldehyde phosphate dehyrdrogenase, phosphoglycerate kinase, phosphoglyceromutase, enolase, pyruvate kinase

Glycolysis in Cytoplasm

glucose, glucose 6-phosphate, fructose 6-phosphate, glyceraldehye 3-phosphate, 1,3-biphosphoglycerate, 3-phosphoglycerate, phosphoenolpyruvate, pyruvate

Glucose Transport

• glycolysis occurs in cytoplasm because all glycolysis enzymes are there

• glucose must enter cell before conversion can occur

• most cells use passive glucose transport protein

• some cells use a specialized uptake system of glucose

Glucose Transport: Passive Transport Protein

• Glut 1, 2, and 4

• transport among the concentration gradient from higher to lower

Enterocytes: Uptake System of Glucose (Glucose Transport)

• sodium glucose linked transporter (SGLT)

  • low Km for glucose (0.3-0.4 mM), transporting glucose or galactose

Glucose Transporter (Glut) 1

• provides baseline glucose uptake, also by Glut 3

• found in many mammalian cells and especially prominent in fetal tissues:

  • highly expressed in placenta, brain, epithelia of mammary glands

• alpha cells in pancreas

• relatively low Km transporter: 1-2 mM

Glut 1: Domains

12 trans-membrane domains: alpha helical segments

Glut 1 Transporting Mechanism

glucose binding on one side induces a conformation change that flips binding site orientation to the other side

Glut 1 Rate Limiting Step

return of unoccupied transporter (active site facing inside), to original face (active site facing outside)