Metabolic Pathways Flashcards
Site of citric acid cycle
Mitochondrial matrix
Major roles of CAC
- Generate ATP by generating reduced carriers for oxidative phosphorylation (NADH and FADH2) and a GTP
- Generate metabolic precursors
Substrate of CAC
Acetyl-CoA
Where can substrate for CAC come from?
From pyruvate (glycolysis), B-oxidation of fatty acids, or ketogenic amino acids
Metabolic product of CAC
Oxaloacetate
Key/entry enzyme of CAC
Citrate synthase (acetyl-CoA + OAA –> citrate)
What are the other important products of the CAC?
3 NADH (formation of α-ketoglutarate, succinyl CoA, and OAA), 1 FADH2 (formation of fumarate), 1 GTP (formation of succinate), 2 CO2 (α-KG and succinyl CoA)
Site of PDH complex
Mitochondrial matrix
Major role of PDH complex
Links glycolysis to CAC
Substrate for PDH complex
Pyruvate
Where does the substrate for PDH complex come from?
Mainly glycolysis, also alanine and lactate
Metabolic product of PDH complex
Acetyl-CoA
Key/entry enzyme for PDH complex
Pyruvate dehydrogenase (PDH) complex
What are the other important products of PDH complex?
1 NADH, 1 CO2 (by decarboxylation)
4 B-vitamins involved in PDH complex reaction
- Riboflavin (B2, FAD)
- Niacin (B3, NAD)
- Thiamin (B1, TPP)
- Pantothenic acid (B5, CoA)
What does deficiency of niacin lead to?
Pellagra (4 D’s)
What does deficiency of thiamin lead to?
Beri-beri (alcoholics, elderly, and low-income)
Lactic acidosis and PDH complex
Decreased complex activity leads to lactate generation
Site of glycolysis
Cytosol
Major role of glycolysis
Generate ATP (and pyruvate)
Substrate of glycolysis
Glucose (and other hexoses)
Metabolic product of glycolysis
Pyruvate (–> lactate in anaerobic conditions or RBCs)
Key/entry enzymes of glycolysis
- Hexokinase (entry)
- Phosphofructokinase (key regulator)
- Pyruvate kinase (forms ATP)
What does deficiency of pyruvate kinase in glycolysis lead to?
Hereditary nonspherocytic hemolytic anemia
What are the other important products of glycolysis?
2 NADH per glucose, 2 net ATP per glucose
What happens after glycolysis in aerobic conditions?
Pyruvate –> acetyl-CoA –> CAC
What happens after glycolysis in anaerobic conditions?
Pyruvate –> lactate to regenerate NAD+
Site of gluconeogenesis
Cytosol (mainly – also mitochondria)
Major role of gluconeogenesis
Generation of blood glucose
Substrates of gluconeogenesis
- Lactate (via pyruvate)
- Glycerol (from TAG breakdown)
- Gluconeogenic amino acids, especially glutamine and alanine
- -Also ODD chain-length fatty acids (NOT acetyl-CoA)
Metabolic product of gluconeogenesis
Glucose
Key/entry enzymes in gluconeogenesis
- Pyruvate carboxylase (pyruvate –> oxaloacetate)
- PEP carboxykinase (OAA –> phosphoenolpyruvate)
- –F1,6-bisphosphatase (F1,6BP –> F6P)*** - G-6-phosphatase (G6P –> glucose)
Which organ does gluconeogenesis mainly occur in?
Liver (kidney in starvation)
Site of glycogenesis
Cytosol
Major role of glycogenesis
Storage of glucose or G6P as glycogen
Substrate of glycogenesis
G6P (from glycolysis)
Metabolic product of glycogenesis
Glycogen
Key/entry enzyme of glycogenesis
Glycogen synthase
How can glycogenesis be inhibited?
By phosphorylation of enzymes in response to hormones
Site of glycogenolysis
Cytosol
Major roles of glycogenolysis
- Supply glucose for ATP generation for contraction (muscle)
- Maintain blood glucose (liver)
Substrate for glycogenolysis
Glycogen
Metabolic product of glycogenolysis
G6P or glucose in liver
Key/entry enzyme of glycogenolysis
Glycogen phosphorylase (forms G1P with Pi)
Site of pentose phosphate pathway
Cytosol
Major roles of PPP
- Form NADPH for biosynthesis
2. Form ribose-5-P for nucleotide synthesis
Substrate of PPP
G6P (from glycolysis)
Metabolic products of PPP
Ribose-5-P, fructose-6-P and glyceraldehyde-3-P (glycolysis), 2 NADPH per glucose
What are the other important products of PPP?
1 CO2 per glucose
Key/entry enzyme of PPP
G6PD (forms NADPH)
What dose deficiency of G6PD lead to?
Hemolytic anemia and Heinz bodies in RBCs
Site of fatty acid B-oxidation
Mitochondrial matrix
Major roles of fatty acid B-oxidation
- Generate acetyl-CoA for ATP production via CAC and oxidative phosphorylation
- Generate FADH2 and NADH for ATP generation via oxidative phosphorylation
Substrate for fatty acid B-oxidation
Fatty acyl-CoA
Metabolic product of fatty acid B-oxidation
Acetyl-CoA
What are the other important products of fatty acid B-oxidation?
FADH2 (2 ATP via ox-phos), NADH (3 ATP)
How does uptake of long chain fatty acids occur in mitochondria?
Facilitation by carnitine
How are fatty acids carried from adipocytes?
By albumin in serum
What types of tissues/organs prefer fatty acids?
Red muscle tissue; anything with abundant mitochondria
Where does B-oxidation of very long chain fatty acids occur initially?
Peroxisomes
What states promote a higher rate of fatty acid B-oxidation?
Fasting/starvation, uncontrolled diabetes, and low carbohydrate diets
Site of fatty acid biosynthesis
Cytosol
Major role of fatty acid biosynthesis
Make fatty acids, mainly for storage
Substrate for fatty acid biosynthesis
Acetyl-CoA (carboxylated to malonyl-CoA)
Metabolic product of fatty acid biosynthesis
Saturated fatty acids, mainly C16 palmitate
What are other important products of fatty acid biosynthesis?
NADP+ from NADPH (2 NADPH required for every 2C) and CO2 from malonyl-CoA
Key/entry enzyme of fatty acid biosynthesis
- Acetyl-CoA carboxylase (acetyl-CoA + CO2 –> malonyl-CoA) – REQUIRES ATP
- Fatty acid synthase complex
What needs to occur with the substrate before fatty acid biosynthesis can occur?
Acetyl-CoA groups are formed in mitochondria – need to be transported to cytosol as citrate and cleaved to acetyl-CoA and OAA
What provides the attachment site in synthase complex of fatty acid biosynthesis?
Phosphopantotheine with -SH group, a derivative of pantothenic acid (vitamin B5)
Site of ketogenesis
Mitochondria
Major role of ketogenesis
Form water-soluble derivatives of fatty acids (ketone bodies) which can serve as important metabolic fuels for many tissues, especially the brain
Substrate for ketogenesis
Acetyl-CoA
Metabolic products of ketogenesis
3 ketone bodies:
- Acetoacetate
- B-hydroxybutyrate
- Acetone
Why would ketogenesis occur?
Spares utilization of glucose and endogenous protein
What states promote higher rate of ketogenesis?
Starvation, poorly controlled diabetes (especially type I), and low carbohydrate diets
What is the reaction catalyzed by pyruvate carboxylase?
Pyruvate –> OAA
What enzymes use biotin?
- -Pyruvate carboxylase
- -Acetyl-CoA carboxylase
What processes occur in the well-fed state?
CAC, glycolysis, PDH complex, glycogenenesis, fatty acid biosynthesis
What processes occur in fasting state?
Gluconeogenesis, glycogenolysis, fatty acid B-oxidation, ketogenesis