Unformatted text preview: Regulation of Cellular Respiration Regulation
in Humans Metabolism Metabolic
Pathways: a summary Balance of all reactions that involve energy transformations.
• Catabolic (“breaking down”): exergonic
– Hydrolysis of polymers into monomers (energy substrates).
– Cellular respiration of energy substrates into CO 2 coupled with
the synthesis of ATP. • Anabolic (“building up”): endergonic
– Dehydration synthesis of polymers for energy-storage or
structure; coupled to the hydrolysis of ATP. Uncoupling Proteins Aerobic Respiration Uncoupling proteins (UCP) in inner mitochondrial membrane of mammals
q Allow some H + leakage, bypassing ATP- synthase .
ß Burn fuel stores without generating ATP
ß May be important in regulating %body fat
ß May also be important in reducing formation of dangerous
Reactive Oxygen Species (ROS)
ßH +-leakage is activated by O 2–.
ßO2– + 2H +Æ H 2O2 Æ H2O + 1/2O2
q In brown (thermogenic )
fat, UCP1 causes heat
generation by burning
high-caloric lipid fuel
without producing ATP Cellular
Metabolism Cellular Metabolism
2. Glucose Glucose 2.
5. = hepatocytes only! Heyer Catabolic pathways:
3. Pyruvate Oxidation
4. Krebs Cycle
6. ß- Oxidation
7. Proteolysis 3. 6. 7. 4.
4. Regulation of Cellular Respiration Cellular Metabolism Glycogenesis and Glycogenolysis 1. Glucose Glucose-6-Phosphate • Glucose-6-phosphate
cannot leak out of the cell.
• Skeletal muscles generate
own glycolytic needs.
• Only Liver contains the
enzyme glucose-6phosphatase that can
remove the phosphate
group and produce free
glucose. 2. 3. Intermediate pathways:
2. Pyruvate Reduction/
3. Deamination = hepatocytes only! Uses of Different Energy Sources ⇑⇑ATP→ inhibits F-6-P-kinase
∴ F-6-P → back to G-6-P
→ alternate pathway → G-1-P
⇑⇑ATP→ inhibits Krebs Cycle
∴ acetyl-CoA → alternate
→ fatty acid synthesis
→ lipogenesis Metabolic Pools Gluconeogenesis & the Cori Cycle
4) 3 5)
6) • Heyer Lactic acid produced by
anaerobic respiration in
muscle is released into the
bloodstream and delivered
to the liver.
LDH converts lactic acid
to pyruvic acid.
(“creating new glucose”)
Pyruvic acid converted
G-6-P can be used either
for 7A- liver glycogenesis
or 7B- can be converted to
free glucose and released into
the bloodstream. 7A 7B 6 & 7B 6 only occur in liver! 2 Regulation of Cellular Respiration Interactions of Liver, Fat & Muscle Maintenance of circulating
• Fasting or low-carbohydrate diet
glucose lactic acid
bodies fatty acids Muscle Fuel Consumption During Exercise
1. 2. 3. 4. 5. At rest: mostly from
aerobic resp. of plama
Start exercise: anaerobic
resp. of plasma glucose;
glycogenolysis. blood flow & O2
delivery ➠ aerobic resp.
of muscle triglycerides.
Gluconeogenesis plasma glucose from
Lipolysis in adipose tissue plama fatty acids for
continued aerobic resp. Krebs Cycle
Oxidation Heyer Lipogenesis
Gluconeogenesis Balance Between Anabolism and Catabolism
• The rate of deposit and
withdrawal of energy
substrates, and the
conversion of one type
of energy substrate into
another; are regulated by
• Antagonistic effects of
insulin, glucagon, GH,
T3, cortisol, and
catabolism. Oxygen Debt
Following anaerobic respiration, increased O2 consumption continues
to support aerobic oxidation of lactate back to pyruvate.
(Reverse of pyruvate reduction. — Uses same LDH enzyme.) Insulin: the primary anabolic hormone Insert fig. 19.4 • glycolysisATP
• lipogenesis 3 Regulation of Cellular Respiration Insulin: the primary anabolic hormone Regulation of Insulin Action
• ↑Blood glucose ⇒ ↑insulin
• ↑Blood amino acids ⇒ ↑insulin ↑Blood amino acids – If high protein/low carb diet ⇒ ↑blood amino acids/↓blood glucose;
⇒ both ↑insulin and ↑glucagon
⇒ ↓blood amino acids without ↓blood glucose • Parasympathetic nervous system: rest-and-digest ⇒ ↑insulin
• Intestinal hormones
– ↑Osm of chyme⇒ ↑GIP/GLP-1/CCK ⇒ ↑insulin
of amino acids Amino Acids ↓Blood amino acids • glycolysisATP Protein • protein synthesis The Catabolic Hormones
— antagonistic to insulin action • “anticipates” ↑blood glucose & amino acids
• ↑insulin faster from ingested glucose than from intravenous glucose! • Adipose hormones
– Enlargement of fat cells ⇒ ↑insulin resistance factor [TNFα]
⇒ ↓insulin sensitivity
• Obesity aggravates diabetes
– Atrophy of fat cells ⇒ ↓TNFα⇒ ↑insulin sensitivity
• Weight loss ⇒ more efficient lipogenesis ⇒ regain lost fat Antagonistic Hormones 1. Glucagon: blood glucose homeostasis
2. Epinephrine: acute stress response
– fight-or-flight 3. Cortisol [glucocorticoid]: chronic stress response
– general adaptation syndrome [GAS]
i. Glucagon and Epinephrine bind to different receptors, but both
receptors produce cAMP as a second messenger. Thus they activate
the same catabolic enzymes producing the same response.
ii. Glucocorticoids bind to an intracellular DNA-binding receptor to
activate genes for a long-term response. Regulation of Insulin and Glucagon Secretion Absorptive & Postabsorptive States Glucagon stimulates catabolic enzymes. Heyer 4 Regulation of Cellular Respiration Diabetes mellitus Diabetes Mellitus:
Type I: destruction of ß-islet cells ⇒ insulin deficiency
Type II: inactivation of insulin receptors ⇒ insulin resistance Type II Diabetes Mellitus Oral Glucose Tolerance Test
• Measurement of the
ability of β cells to
• Ability of insulin to
• Normal person’s
rise in blood
drinking solution is
reversed to normal
in 2 hrs. Insert fig. 19.8 cAMP-mediated Catabolic Response Heyer • Slow to develop.
• Genetic factors are
• Occurs most often in
people who are
• Decreased sensitivity to
insulin or an insulin
resistance. Insert fig. 19.12 – Obesity. • Do not usually develop
• May have high blood
[insulin] or normal
[insulin]. Chronic Stress Response 5 Regulation of Cellular Respiration Glucocorticoids work via nuclear receptors:
change gene expression / long term effects Other Important Metabolic Hormones • Thyroxine Growth Hormone
protein anabolism Synopsis of metabolic hormone action – Adjusts basal metabolic rate (BMR)
• Makes electron transport system less efficient at producing ATP.
• Cells must ⇑glycolysis & ß-oxidation to meet energy demands.
“Wasted” energy released as heat. – Very important in juvenile development to stimulate growth and
mental development. • Anabolic Steroids (androgens) – At puberty, stimulates protein synthesis for enhanced growth of
muscle, bones, and secondary sexual characteristics.
• But also stimulates final maturation of bones, preventing further growth. • Chorionic Somatomammotropin (hCS) – Produced by the placenta. GH-like and Prl-like activity.
– GH-like activity: ⇑lipolysis / ⇓glucose utilization in maternal
tissues ⇒ ⇑blood fatty acids & glucose available to the fetus.
• “Diabetes of pregnancy” – Prl-like activity: Also stimulates growth of mammary glands. Heyer 6 ...
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