METABOLISMEdited by Liniyanti D.Oswari,MD.MSc.

Metabolism = all chemical reactionsin the body

Two Basic Types of ReactionsAnabolic = build large molecules from small unit

moleculesRequire energy

Catabolic = breakdown large molecules into small unit moleculesRelease energy

Oxidation Reaction = remove electrons and/or H+ from a molecule

Electron plus H+ = ??

Anabolic or Catabolic ??

Requires Energy or Releases Energy ??

Reduction Reaction = add electrons and/or H+ to a molecule

Electron plus H+ = ??

Anabolic or Catabolic ??

Requires Energy or Releases Energy ??

Phosphorylation Reaction = add phosphate (PO4

-3 ) to a moleculeAnabolic or Catabolic ??

Requires Energy or Releases Energy ??

Dephosphorylation = Removing a Phosphate (PO4

-3 ) Anabolic or Catabolic ??

Requires Energy or Releases Energy ??

The ATP Cycle

In cells when a Hydrogen (H) or an electron is removed (oxidation) it goes immediately to another molecule (reduction)

When energy is released (oxidation) it goes to another molecule (reduction)

Combination = oxidation-reduction reactionor Redox reaction

Cells keep some molecules around just to accept H, electrons & energy from oxidation reaction (to be reduced)

Adding H, electrons & energy to these molecules would be a reduction reaction

One common group of these molecules are the coenzymes

Two examples are NAD+ and FAD

CoenzymesNAD+ + H+ + 2 electrons + Energy NADH

Identify the reduced coenzyme?Identify the oxidized coenzyme?Which form of coenzyme has more energy?

FAD + 2H+ + 2 electrons + Energy FADH2

Identify the reduced coenzyme?Identify the oxidized coenzyme?Which form of coenzyme has more energy?

ENERGY FLOW

Glucose Coenzyme ATP Oxidation Reduction Oxidation Phosphorylation

ENERGY ENERGY

ALL Reactions are controlled by ENZYMES

Gut-Brain Peptides(only a few out of many)

Chemical signals from the G.I. Tract to the Brain

Short-term Regulators• Last for minutes to hours• Make us want to start eating and stop eating

Long-term Regulators• Work over periods of weeks to years• Regulate our caloric intake & energy spent and

amount of adipose tissue

Short-Term RegulatorsGhrelin• Secreted from parietal cells when stomach empty

& stops within an hour of eating• Produces sensation of hunger & starts up eating• Causes hypothalamus to release GHRH (↑ hGH)

Peptide YY• Secreted by ileum & colon in response to food in

the stomach, in proportion to calories consumed• Signals satiety & stops eating

Cholecystokinin• Secreted by duodenum & jejunum• Produces appetite-suppressing effect via Vagus N.

Long-Term Regulators

Leptin• Secreted by adipocytes in proportion to amount of

stored fat• Primary way brain knows how much body fat is

stored• Obesity is related to receptor unresponsiveness

Insulin• Secreted by beta cells in pancreas• Stimulates glucose & amino acid uptake• Promotes glycogen & fat synthesis• Additional way brain knows how much body fat is

stored (effect weaker than leptin)

The Arcuate Nucleus of the Hypothalamus is the primary appetite regulation center in the brain

Secretes Neuropeptide Y = Appetite Stimulant• Ghrelin stimulates secretion• Peptide YY, leptin & insulin inhibit secretion

Secretes Melanocortin = Appetite Suppressant• Leptin stimulates secretion

Carbohydrate Metabolism

Monosaccharides absorbed;• Glucose• Fructose• GalactoseFructose & Galactose are converted to glucose

in the liverCarbohydrate metabolism =

Glucose metabolism

1) Glucose enters cells & is oxidized for energy= Cellular Respiration

Aerobic or Anaerobic

Aerobic Cellular Respiration

C6H12O6 + 6O2 6CO2 + 6H2O

Glycolysis

Net Production of Energy Molecules

Per Glucose;2 ATP2 NADH

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Transition ReactionPer Glucose;2 NADH

Kreb’s (Citric Aid) CyclePer Glucose;2 ATP6 NADH2 FADH2

Per Acetyl CoA ??

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ENERGY FLOW

Glucose Coenzyme ATP Oxidation Reduction Oxidation Phosphorylation

ENERGY ENERGY

ALL Reactions are controlled by ENZYMES

Electron Transport System

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Oxidize NADH = 3 ATPOxidize FADH2 = 2 ATP

Electron Transport SystemOxidize NADH = 3 ATPOxidize FADH2 = 2 ATP

Glycolysis 2 NADH X 3 = 6 ATPTrans Rx 2 NADH X 3 = 6 ATPKreb’s6 NADH X 3 = 18 ATP

2 FADH2 X 2 = 4 ATP

TOTAL 34 ATP

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Only 2 ATP per Glucose

What happened to 2 NADH ?

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Anaerobic Cellular Respiration= Glycolysis only

2) Excess glucose is stored as glycogen• Most (~80%) in skeletal muscle• Remainder in liverAnabolic Rx: glucose glycogen = glycogenesisCatabolic Rx: glycogen glucose = glycogenolysis

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3) If glycogen storage is full, glucose stored as lipids (triglycerides) in adipose tissue

Triglyceride

Triglyceride

Glucose transformed into Triglyceride

Glucose PGAL Glycerol

Acetyl CoA Fatty Acids (beta reduction Rx)

Glycerol + 3 Fatty Acids Triglyceride

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4) Excess glucose may be excreted in urine

Glucose is considered an abnormal component of urine, but with very high concentrations in blood the kidneys cannot keep some glucose from leaving the body

Sodium-glucose transport proteins get overwhelmed

Diabetes Mellitus = cells can’t uptake glucose, so concentrations remain very high in blood, causing glucose to end up in the urine

Lipid Metabolism

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CHYLOMICRON PATHWAY: Chylomicrons absorbed from intestines into lymphatic system & ultimately the bloodstream. Endothelial cell surface enzyme, lipoprotein lipase, hydrolyzes triglycerides into monoglycerides & free fatty acids.

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VLDL/LDL PATHWAY: Very low-density lipoproteins (VLDL) transport lipids from liver to adipose for storage. Triglycerides are stored in adipose, leaving low-density lipoproteins (LDL) that contain mostly cholesterol. LDLs enter cells that need cholesterol.

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HDL PATHWAY: High-density lipoproteins (HDL) leave liver as empty protein shells that pick up cholesterol & phospholipids. As HDLs pass through liver, cholesterol is removed & liver removes as cholesterol and bile acids.

Chylomicron Pathway =triglycerides from intestine to body cells

VLDL / LDL Pathway = 1st STOP: triglycerides from liver to adipose

2nd STOP: cholesterol from liver to body cells

HDL Pathway = cholesterol from blood to liver

1) Lipids are taken up by the body cells for non-energy uses

• Cell membrane phospholipids, steroid hormones, etc.• Delivered by chylomicrons & VLDL/LDLs from liver

2) Much of the lipids are stored as triglycerides in adipose tissue & the liver.

• Delivered by chylomicrons & VLDL/LDLs from liver

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3) If blood glucose is low, triglycerides can be released from the adipose to be oxidized for energy.

Beta-oxidationof fatty acids

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Each beta oxidation reaction releases enough free energy to produce 5 ATPs

An 18-carbon fatty acid can produce nine2-carbon Acetyl CoA

How many beta oxidations does it take ?

A beta oxidation reaction removes one acetyl group (-COCH3) from a fatty acid to make one Acetyl CoA

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Each Acetyl CoA can then enter into the Citric Acid Cycle

How many energy molecules will be produced for each Acetyl CoA?

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The liver can combine two acetyl groups into one of three compounds called ketone bodies, which are released into the blood.

Cells in heart and brain use ketone bodiesto make Acetyl CoA which then enter the Citric Acid Cycle.

Protein Metabolism

Amino acids are absorbedfrom the small intestine

About 50% from diet

About 25% from dead epithelial cells

About 25% from digested enzymes

1) Amino acids used for protein synthesis

Amino acids can be actively transported into body cells & used to build proteins

What are someexamples of proteins?

20 different amino acids are used to synthesize proteins

About half are called essential amino acids because they must come from the diet

Foods that contain all the essential amino acids are called complete proteins, for example; eggs, milk, meat.

The nonessential amino acids can be produced by the body through a process called transamination

Transamination = transfer of an amino group (NH2) from an abundant amino acid to a keto acid to make a new amino acid

Keto acid + amino group (NH2) amino acid

2) Amino acids can be used as fuel, or a source of energy

First step is deamination, which is removal of an amino group (NH2) from an amino acid creating a keto acid

Amino acid Keto acid + amino group (NH2)

Depending on which amino acid is deaminated,

the keto acid may be converted to;

• Pyruvic acid• Acetyl CoA• One of the acids of citric

acid cycle

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Pyruvic acid could be converted back into glucose by cells in the kidney or liver

This is an example of gluconeogenesis, which is making glucose from a non-carbohydrate source

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The amino group is transferred to α–ketoglutaric acid, making glutamic acid, that travels to the liver & is converted back to α–ketoglutaric acid

Left over ammonia (NH3) is converted to urea

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Absorptive State = 4 hours during & after a mealNutrients are being absorbed & then immediately used or stored

Postabsorptive State = stomach & intestine are emptyStored fuel molecules are used for energy