Module 5-6 Review Flashcards
Fed state fuel for the liver
(Fuel,Transport; Pathways (2))
Glucose (GLUT2; glycogenesis, lipogenesis)
Fasted state fuel for liver
Glucose via glycogenolysis/gluconeogenesis
NO KETONE BODIES
Fed state fuel and function of adipose tissue
Glucose
Lipogenesis/fatty acid storage
Fasting state fuel for adipose
Free fatty acids via lipolysis
Fed state fuel for muscle
Glucose (GLUT4; glycogenesis)
Fasting state fuel for muscle
Fatty acids (oxidation), amino acids (prolonged fasting)
Fed state fuel for brain and what are the membrane uptake proteins
Glucose (GLUT3 and GLUT1)
Fasting state fuel for brain
Glucose, ketone bodies (during prolonged fasting)
Fed state fuel for heart
Fatty acids (circulating lipids)
Fasting state fuel for heart
Glucose, lactate, pyruvate. Prolonged fasting:
ketone bodies
Fed state fuel for RBC
Glucose (GLUT2)
Fasting state fuel for RBC
Glucose (hepatic glycogenolysis; gluconeogenesis
What does caffeine inhibit
cAMP phosphodiesterase, resulting in PKA activation and glucagon and epinephrine enhanced response
Glucagon additional effects
Promote gluconeogenesis by increasing PKA, which decreases f-2,6-bisphosphate and activates f-1,6-bisphosphate and glycogenolysis in the liver
Which diabetes type will likely show ketoacidosis
Type 1
Symptoms and treatment of ketoacidosis
Polyuria, dehydration, thirst, CNS depression and coma, potential depletion of K+, decreased plasma bicarbonate, dry mucous membranes, breathing difficulties, sweet/fruity breath (acetone), increased acetoacetate (ketone bodies) in the urine. Treating with insulin will stimulate glucose uptake to muscle and adipose tissue from the blood and reduce
hyperglycemia and control ketoacidosis
What steps and enzymes of glycolysis are energy used
1 - Hexokinase
3 - Phosphofructokinase-1
What steps and enzymes of glycolysis are energy released
6 - Glyceraldehyde 3-phosphate dehydrogenase (NADPH)
7 - Phosphoglycerate kinase (ATP)
10 - Pyruvate kinase (ATP)
Pyruvate kinase deficiency leads to
Hemolytic anemia with increased serum 2,3-
BPG levels and reduced ATP production
What are the enzymes in the Luebering-Rapoport Shunt
Bisphosphoglycerate mutase
Bisphosphoglycerate phosphotase
What does bisphosphoglycerate mutase do
1,3-diphosphoglycerate to 2,3-diphosphoglycerate in LR shunt
What does bisphosphoglycerate phosphatase do
2,3-diphosphoglycerate to 3-phosphoglycerate in LR shunt
What is the main enzyme in Methemoglobin Reductase Pathway
Cyt b5 reductase
G6PD deficiency leads to
hemolytic anemia and prolonged neonatal jaundice due to inability of generating NADPH and pentose sugars. G6PD deficiency provides resistance against malarial infection
Pyruvate kinase deficiency leads to
Hereditary hemolytic anemia, increased serum 2,3-BPG levels
In what ways besides glycolysis is dihydroxyacetone phosphate (DHAP) involved
AP reduced to glycerol-3-
phosphate (forms glycerol backbone in triglycerides); in gluconeogenesis, it is converted to glyceraldehyde-3-phosphate
What activates pyruvate carboxylase and what does PC do
Acetyl Coenzyme A
Catalyzes irreversible
carboxylation of pyruvate to form oxaloacetate. Involved in gluconeogenesis and synthesis of neurotransmitters such as
glutamate.
Deficiency of pyruvate carboxylase leads to
an inherited disease that causes lactic acid and other toxic compounds to accumulate in the blood.
The deficiency of this enzyme also causes a decrease in citrate, aspartate, and phosphoenolpyruvate levels as these compounds are formed from oxaloacetate.
What enzyme and coenzyme are associated with E1
Pyruvate dehydrogenase (coenzyme: Thiamine pyrophosphate/B1)
What enzyme and coenzyme are associated with E2
Dihydrolipoyl transacetylase (coenzymes: Lipoamide, Coenzyme A) (B5)
What enzyme and coenzyme are associated with E3
Dihydrolipoyl dehydrogenase (coenzymes: Flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NAD+) (B2/B3)
Symptoms of and prognosis of pyruvate dehydrogenase reduced activity
Arsenic poisoning
Lactic acidosis, headaches, confusion, convulsions and heart diseases. Arsenic poising can also lead to squamous cell carcinoma
PDH reduced activity can be due to
Wernicke-Korsakoff (encephalopathy-psychosis syndrome due to thiamine deficiency seen with alcohol abuse)
Symptoms of Wernicke-Korsakoff
Lactic acidosis, neurological disturbances, paralysis, atrophy of limbs and cardiac failure
What is succinate dehydrogenase gene deficiency
Homozygous and
heterozygous mutations in the subunits of SD
Types of succinate dehydrogenase gene deficiency
SDHA: Leigh syndrome (it could also be due to PDH deficiency)
SDHB and SDHD: Paraganglioma and pheochromocytoma
SDHC: Paraganglioma
Most common features of succinate dehydrogenase gene deficiency
Leigh syndrome, hypertrophic cardiomyopathy, muscle
weakness, cerebral ataxia, optic atrophy
What is fumarase gene deficiency
Inherited autosomal recessive disease
Symptoms of fumarase gene deficiency
Affects nervous system
Infants may have an
abnormally small head size, abnormal brain structure, developmental delay, and weak muscle tone, face frontal bossing, depressed nasal bridge, and widely spaced eyes
What is succinyl-CoA synthetase gene deficiency
Homozygous and heterozygous mutations in the subunits of SUCLA1 and 2
What is the importance of succinyl-CoA synthetase
Succinyl-coenzyme A
is an intermediate in the TCA cycle and is also a substrate of heme synthesis. Succinyl-coenzyme A and glycine are combined in the first step of heme synthesis to form aminolevulinic acid. In
the Krebs cycle, succinyl-coenzyme A is an intermediate generated by α-ketoglutarate dehydrogenase.
Most common symptoms of succinyl-CoA synthetase gene deficiency
Ecephalomyopathy, developmental delay,
dystonia, and lactic acidosis
Main function of complex I (NADH Oxidoreductase)
Transfers electrons from NADH to ubiquinone (CoQ), pumps protons to generate proton gradient
Main function of complex II (succinate dehydrogenase)
Transfers electrons from FADH2 to ubiquinone (CoQ), does not pump protons (Part of TCA cycle also)
Main function of complex III (Ubiquinone-Cytochrome c
Oxidoreductase)
Transfers electrons from ubiquinone to cytochrome c, pumps protons
Main function of ATP Synthase
Uses the proton gradient created by ETC to synthesize ATP from ADP + inorganic phosphate
Key inhibitor of complex II (succinate dehydrogenase)
Malonate
Key inhibitor of complex III (Ubiquinone-Cytochrome c
Oxidoreductase)
Antimycin A
Key inhibitor of complex IV (Cytochrome c Oxidase)
Cyanide
Key inhibitor of ATP Synthase
Oligomycin
Physiological relevance of uncoupling
Thermogenesis: UCP1 in brown adipose tissue mediates heat production to maintain body temperature in cold environments
Pathological relevance of uncoupling
Overuse of uncoupling agents (e.g., DNP, FCCP overdose) can cause hyperthermia, metabolic disturbances, and potentially death
What is the MOA of 2,4-Dinitrophenol (DNP)
Protonophore that carries protons across the inner
mitochondrial membrane, dissipating the proton gradient and uncoupling oxidative phosphorylation, and heat production
What is the MOA of uncoupling Proteins (UCPs)
Proteins (e.g., UCP1, UCP2, UCP3) that allow protons to re-enter the mitochondrial matrix without producing ATP, leading to heat generation (thermogenesis).
What is carbonyl cyanide-p-
trifluoromethoxyphenylhydrazone (FCCP)
An ETC uncoupling agent
Medical use for 2,4-Dinitrophenol (DNP)
Historically used for weight loss (no longer used due to toxicity, including hyperthermia and fatality)
Medical use for uncoupling proteins (UCPs)
UCP1 is involved in non-shivering thermogenesis in brown adipose tissue
Pyruvate carboxylase cofactor in gluconeogenesis
Biotin (B7)
How is pyruvate carboxylase activated in gluconeogenesis
Acetyl-CoA
Process that pyruvate carboxylase is involved in in gluconeogenesis
Pyruvate to oxaloacetate (requires malate shuttle into cytosol)
Phosphoenolpyruvate carboxykinase (PEPK) cofactor in gluconeogenesis
GTP
What activates phosphoenolpyruvate carboxykinase (PEPK) in gluconeogenesis
Glucagon
Cortisol
Process that phosphoenolpyruvate carboxykinase (PEPK) is involved in in gluconeogenesis
OAA to phosphoenolpyruvate (PEP) (PEP to fructose-1,6-bisphosphate)
Rate limiting step of gluconeogenesis
Fructose-1,6-phosphate to fructose-6-phosphate
Fructose-1,6-bisphosphatase cofactor in gluconeogenesis
ADP
What activates/deactivates fructose-1,6-bisphosphatase in gluconeogenesis
ATP
AMP and fructose-2,6-phosphate
What is nonreversible in gluconeogenesis
Glucose-6-Phosphate to glucose
What does glucose-6-phosphatase do
Glucose-6-Phosphate to glucose
Where is glucose-6-phosphatase active
Liver
Role of fructose 2,6-bisphosphate in gluconeogenesis
Controls gluconeogenesis and glycolysis in the liver
What produces fructose 2,6-bisphosphate
PFK-2
What activates/deactivates PFK-2
Insulin
Glucagon
Glucagon lowers _______ stimulating ________
Fructose-2,6-bisphosphate
Gluconeogenesis
Insulin increases _______ stimulating ________
Fructose-2,6-bisphosphate
Gluconeogenesis
Rate limiting step of glycogen synthesis
Glycogen synthase
What does glycogen synthase do
Catalyzes the addition of UDP-glucose to the growing glycogen chain, forming α-1,4-glycosidic bond
Rate limiting step of glycogenolysis
Glycogen phosphorylase
What does glycogen phosphorylase do
Catalyzes the cleavage of α-1,4-glycosidic bonds, releasing glucose-1-phosphate (G1P) from
glycogen
