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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
p 1014
Transition ReactionPer Glucose;2 NADH
Kreb’s (Citric Aid) CyclePer Glucose;2 ATP6 NADH2 FADH2
Per Acetyl CoA ??
p 1016
ENERGY FLOW
Glucose Coenzyme ATP Oxidation Reduction Oxidation Phosphorylation
ENERGY ENERGY
ALL Reactions are controlled by ENZYMES
Electron Transport System
p 1018
p 1017
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
p 1019
Only 2 ATP per Glucose
What happened to 2 NADH ?
p 1014
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
p 1020
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
p 1022
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
p 1009
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.
p 1009
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.
p 1009
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
p 1022
3) If blood glucose is low, triglycerides can be released from the adipose to be oxidized for energy.
Beta-oxidationof fatty acids
p 1022
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
p 1022
Each Acetyl CoA can then enter into the Citric Acid Cycle
How many energy molecules will be produced for each Acetyl CoA?
p 1022
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
p 1023
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
p 1023
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
p 1023
p 1025
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