Metabolism and Energetics

further notes on nutrition & metabolism

Release of energy from food

coupled reactions

free energy

ΔF for oxidation of 1 mol glucose = 686 kcal

Role of ATP in metabolism

at STP ~-bond ΔF = 7.3 kcal, but 12 kcal at body conditions

Role of glucose in carbohydrate metabolism

glucose metabolism

Transport of glucose through the cell membrane

facilitated diffusion

active sodium cotransport

GI cell membrane

renal tubule membrane

facilitation of glucose transport by insulin

phosphorylation of glucose

glucokinase in liver

hexokinase elsewhere

Storage of glycogen in liver and muscle

glycogenesis

g6p → g1p → UDPg

sources include convertible monosaccharides

lactic acid, glycerol, pyruvic acid, some amino acids

glycogenolysis

activation of phosphorylase by Epi and glucagon

increase of cAMP

Release of energy from glucose molecule by the glycolytic pathway 1

glucose + 2 ADP + 2 PO43- → 2 pyruvic acid + 2 ATP + 4 H

amount of energy lost from glucose, 56 kcal, efficiency 43%

Conversion of pyruvic acid to acetyl-CoA

2 pyruvic acid + 2 CoA → 2 Acetyl-CoA + 2 CO2 + 4 H

Citric acid cycle 2

2 Acetyl-CoA + 6 H2O + 2 ADP → 4 CO2 + 16 H + 2 CoA + 2 ATP

Formation of ATP by oxidative phosphorylation 3

chemiosmotic mechanism of the mitochondria

ionization of hydrogen

2 H + NAD+ → NADH + H+

electron transport chain

flavoprotein, ubiquinone, cytochromes

cytochrome A3, cytochrome oxidase

ATP synthase

Control of glycolysis and oxidative phosphorylation by ATP and ADP

allosteric inhibition of phosphofructokinase

excess citrate

Anaerobic glycolysis

formation of lactic acid

reconversion of lactic and pyruvic acids to glucose

expenditure:  6 ATP

Phosphogluconate pathway

glucose + 12 NADP+ + 6 H2O → 6 CO2 + 12 H + 12 NADPH

5 for 6

Transport of lipids in the blood

lipoproteins

Protein metabolism

nonessential and essential amino acids

ATP

synthesis of cellular components

muscular contraction

membrane active transport

glandular secretion

nerve conduction

Phosphocreatine and ATP

~-bond contains 8.5 kcal at STP, 13 kcal at body conditions



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Nutrition and Metabolism

Nutrition

nutrients

major nutrients

kilocalories (kcals)

essential nutrients

Carbohydrates

complex carbohydrates (starch)

monosaccharides (simple sugars)

Lipids

triglycerides

essential fatty acids - linoleic and linolenic acid

dietary requirements

phospholipids

prostaglandins

cholesterol

Proteins

complete proteins

dietary requirements

incomplete proteins

essential amino acids

daily intake

synthesis and hydrolysis

all-or-none rule

nitrogen balance

hormonal control

anabolic hormones accelerate protein synthesis

Vitamins

only vitamins D, K, and B are synthesized in the body

water-soluble vitamins (B-complex and C)

fat-soluble vitamins (A, D, E, and K)

bind to ingested lipids and are absorbed with their digestion products

Minerals

seven minerals are required in moderate amounts

calcium, phosphorus, potassium, sulfur, sodium, chloride, and magnesium

at least a dozen are required in trace amounts

Metabolism

cellular respiration

anabolic reactions

catabolic reactions

stages of metabolism

digestion

anabolism

oxidative breakdown

oxidation-reduction (ReDox) reaction

oxidized substances lose energy

reduced substances gain energy

coenzymes

nicotinamide adenine dinucleotide (NAD+)

flavin adenine dinucleotide (FAD)

substrate-level phosphorylation

glycolysis and the Krebs cycle

oxidative phosphorylation

is carried out by the electron transport proteins in the cristae of the mitochondria

Carbohydrate Metabolism

oxidation of glucose:

c6H12O6 + 6O2 → 6H2O + 6CO2 + 36ATP + heat

three pathways

glycolysis

citric acid (Krebs) cycle

electron transport chain and oxidative phosphorylation

Glycolysis

a three-phase pathway:

glucose is oxidized into pyruvic acid

NAD+is reduced to NADH + H+

ATP is synthesized by substrate-level phosphorylation

pyruvic acid:

moves on to the Krebs cycle

reduced to lactic acid

glycolysis:  phases 1 and 2

sugar activation

two ATP molecules activate glucose into
fructose-1,6-diphosphate

sugar cleavage 

dihydroxyacetone phosphate

glycolysis:  phase 3

oxidation and ATP formation

final products: 

two pyruvic acid molecules

two reduced NAD+ (NADH + H+) molecules

net gain of two ATP molecules

Krebs Cycle

preparatory steps

occurs in mitochondrial matrix

pyruvic acid is converted to acetyl CoA in steps:

decarboxylation

oxidation

formation of acetyl CoA

an eight-step cycle in which acetic acid is decarboxylated and oxidized, generating (times 2!): 

three molecules of NADH + H+

one molecule of FADH2

two molecules of CO2

one molecule of ATP

Electron Transport Chain

food (glucose) is oxidized and the hydrogens:

are transported by coenzymes NADH and FADH2

enter a chain of proteins bound to metal atoms (cofactors)

combine with molecular oxygen to form water

release energy

hypothetical mechanism of oxidative phosphorylation

NADH dehydrogenase (FMN, Fe-S)

cytochrome b-c1

cytochrome oxidase (a-a3)

ATP synthase

electron energy gradient

NADH + H+ and FADH2

glycogenesis

glycogenolysis

gluconeogenesis

Lipid Metabolism

chylomicrons

lipids in chylomicrons are hydrolyzed by plasma enzymes and absorbed by cells

catabolism of fats involves two separate pathways

glycerol pathway

glycerol converted to glyceraldehyde phosphate

fatty acid pathway

fatty acids undergo beta oxidation

glyceraldehyde converted into acetyl CoA

acetyl CoA enters the Krebs cycle

lipolysis

ketone bodies

synthesis of structural materials

phospholipids

by the liver:

synthesizes lipoproteins for transport of cholesterol and fats

makes tissue factor, a clotting factor

synthesizes cholesterol for acetyl CoA

uses cholesterol for forming bile salts

certain endocrine organs use cholesterol for synthesizing steroid hormones

Protein Metabolism

oxidation of amino acids

transamination

α-ketoglutaric acid

glutamic acid

oxidative deamination

keto acid modification

Catabolic-Anabolic Steady State of the Body

Absorptive State

anabolism and energy storage

principal pathways

muscle

liver

adipose tissue

insulin effects on metabolism

stimulated by:

increased blood glucose

elevated amino acid levels in the blood

gastrin, CCK, and secretin

effects

diabetes mellitus

Postabsorptive State

catabolism and replacement of fuels in the blood

glycogenolysis and gluconeogenesis

principal pathways

muscle

liver

hormonal and neural controls

alpha cells of pancreas secrete glucagon

glycogenolysis and gluconeogenesis

glucose sparing

sympathetic nervous system releases epinephrine

Metabolic Role of the Liver

cholesterol

structural basis of bile salts, steroid hormones, and vitamin D

directs embryonic development

transported via lipoproteins

HDLs -
high-density lipoproteins have more protein content

LDLs -
low-density lipoproteins have a considerable cholesterol component

VLDLs -
very low density lipoproteins are mostly triglycerides

Energy Balance

Regulation of Food Intake

Metabolic Rate

rate of energy output

measured directly with a calorimeter or indirectly with a respirometer

basal metabolic rate (BMR)

expressed in kcal/m2/h

total metabolic rate (TMR)

factors that influence BMR



Questions for thought
1.   What is oxidative phosphorylation? What is the role of the electron transport system in this process?
2.   How are lipids broken down? How is beta-oxidation involved with lipid catabolism?
3.   How do the absorptive and post-absorptive states maintain normal blood glucose levels?
4.   Why are vitamins and minerals essential components of the diet?
5.   Many articles in popular magazines refer to “good cholesterol” and “bad cholesterol”. To which types and functions of cholesterol might these terms refer? Explain your answer.
6.   Describe the major events and outcomes of glycolysis.
7.   Pyruvic acid is a product of glycolysis, but is not the substance that enters the citric acid cycle. What is the substance, and what must occur if pyruvic acid is to be transformed into that molecule.