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Biology 219 – Human Physiology
Clemens
Cellular Metabolism - Part 1
Text: Ch 4
A. Cellular Respiration - metabolism of substrates to release energy to form ATP
ATP
Oxidation of glucose:
glucose + 6 O2 → 6 CO2 + 6 H2O + energy
heat
1. Glycolysis
- partial breakdown of glucose to pyruvate: glucose → 2 pyruvate
- occurs in the cytosol
- multi-step pathway
a. energy investment steps - add 2 high-energy phosphates from ATP
b. cleavage step - splits 6C sugar into two 3C molecules
c. energy capture steps - yield 2 NADH and 2 ATP
Each NADH carries 2 high-energy electrons:
NAD+ + 2 H → NADH + H+
oxidized
reduced
- pyruvate is the branch point between aerobic and anaerobic metabolism of glucose
Aerobic metabolism - pyruvate goes to Transition Step and Citric Acid Cycle in the mitochondria
- NADH donates electrons to the Electron Transport Chain
yield: 2 ATP + 2 NADH per glucose
product (intermediate): 2 pyruvate
Anaerobic metabolism - pyruvate converted to lactate via the lactic acid pathway in the cytosol
pyruvate + NADH → lactate + NAD+
- NADH is converted back to NAD+ needed to continue glycolysis
yield: 2 ATP per glucose
product: 2 lactate + 2 H+
2a. Transition Step from Glycolysis to the Citric Acid Cycle:
pyruvate (3C) + CoA + NAD+ → acetyl CoA (2C) + CO2 + NADH
yield: 1 NADH (x 2)
product: 1 CO2 (x 2)
acetyl CoA is a key intermediate which transfers 2C units to the Citric Acid Cycle
2b. Citric Acid (Krebs) Cycle
- complete oxidation of 2C units from acetyl CoA → 2 CO2
- occurs in the matrix of the mitochondria
- multi-step sequence of redox reactions
first step: acetyl CoA (2C) + oxaloacetate (4C) → citrate (6C) + CoA
subsequent steps: citrate is converted back to oxaloacetate,
- 2 C atoms are fully oxidized to form 2 CO2 molecules
- high-energy electrons are transferred to NADH and FADH2 (reduced coenzymes)
yield: 3 NADH + 1 FADH2 + 1 ATP (x 2)
product: 2 CO2 (x 2)
3. Electron Transport Chain
- electron carrier proteins are located in the inner membrane of the mitochondria
3 major protein complexes (I, III, IV)
cytochromes - iron-containing proteins in the E.T.C.
- NADH and FADH2 donate high-energy electrons to the E.T.C.
- electrons move “downhill” through E.T.C., release energy for ATP production
- oxygen (O2) is the final electron acceptor: ½ O2 + 2 e- + 2 H+ → H2O
4. ATP Synthesis
Chemiosmotic Coupling mechanism:
- E.T.C. complexes act as H+ pumps
- H+ is pumped “uphill” from the matrix into the intermembrane space containing high [H+]
- H+ moves back “downhill” through the ATP synthase in the inner membrane
- ATP synthase phosphorylates ADP to ATP
Complete oxidation of glucose:
yield: ~ 30 ATP per glucose
end products: 6 CO2 + 6 H2O
Biology 219 – Human Physiology
Cellular Metabolism - Part 2
Clemens
Text: Ch. 4 and 22
B. Glycogen Metabolism
1. Glycogen synthesis (glycogenesis)
glucose + ATP → glucose-6-P → glycogen
- glycogen is stored mostly in liver and skeletal muscle cells
- the hormone insulin stimulates glycogen synthesis when blood [glucose] is high
2. Glycogen breakdown (glycogenolysis)
glycogen + Pi → glucose-6-P → glucose
- in liver: glycogen → glucose → released into blood to maintain glucose homeostasis
- the hormone glucagon stimulates glycogenolysis in liver when blood [glucose] is low
- in skeletal muscle: glycogen → glucose-6-P → metabolized in active muscle cells
C. Protein Metabolism
1. Proteolysis
a. Protein catabolism
- hydrolysis of polypeptides → amino acids
b. Deamination - removal of the amino group
amino acids → keto acids + NH3 (ammonia)
keto acids enter the Citric Acid Cycle → CO2 + H2O + energy
NH3 is converted to urea → excreted by the kidneys
(transamination: -NH2 group is transferred to another amino acid)
2. Protein Synthesis (will cover later)
3. Tissue Utilization of Proteins
- normal protein turnover in cells
- protein metabolism increases during starvation, injury, heavy exercise, high-protein diet
D. Fat Metabolism
1. Lipolysis - catabolism of fats and other lipids
a. Hydrolysis of triglycerides
triglyceride + H2O → fatty acids + glycerol
b. Beta oxidation - stepwise oxidation of fatty acids
- fatty acids are broken down into 2C units → acetyl CoA → Krebs Cycle → CO2 + H2O
- high energy yield: >100 ATP per fatty acid
> 2X more energy yield per gram than carbohydrates
2. Lipid Synthesis
- fatty acids are synthesized from 2C units of acetyl CoA
- fatty acids are combined with glycerol to form triglycerides and phospholipids
3. Tissue Utilization of Fatty Acids
- triglycerides are stored mostly in adipose tissue
- lipids are transported in the blood by lipoproteins: HDL, LDL
- liver, heart, and resting skeletal muscle use mostly fatty acids for energy
- fatty acids are broken down only by aerobic metabolism
- excessive fat catabolism → formation of ketone bodies (→ metabolic acidosis)
E. Gluconeogenesis
= formation of glucose from non-carbohydrate sources: amino acids, glycerol, lactate
- occurs mostly in the liver
- important during fasting or glucose depletion (e.g., exercise, stress, low carbo diet)
- stimulated by hormones cortisol and glucagon
F. Interconversion of Substrates
glucose → acetyl CoA → fatty acids (lipid synthesis)
amino acids → keto acids → glucose (gluconeogenesis)
glucose → keto acids → amino acids (transamination)
(Note: fatty acids can not be converted into glucose or amino acids)