BIOCHEMICAL INTEGRATION

SHEET OF PAPER

Insulin- polypeptide hormone secreted by the beta cells of the islets of Langerhans in the
endocrine pancreas
-stimulated by rise in blood glucose
-inhibited by epinephrine

- Has intrinsic tyrosine kinase (secondary messenger)

Effects (anabolism, catabolism)

Increased
Glucose Uptake
Glycogenesis
Synthesis of protein and fat

Decreased
Glycogenolysis

Glucagon- polupeptide hormone alpha cells

-stimulated by low blood glucose, AA, epinephrine
-inhibited by high blood glycose, insulin
G-proteins that activate adenylate cyclase to increase to imprease Camp and protein A

BOTH KETOGENESIS AND KETOLYSIS OCCUR IN THE FASTING STATE!

Low blood sugar (glucose <40 mg/dL)

Hromones glucagon and epinephrine
Decreased insulin

Manifestation: tachycardia, tremors, diaphoresis

Neuroglycopenic: confusion, seizures, coma
Quick resolution of symptoms after administration of glucose

FEED FAST DIAGARAM (LIPPINCOTT)

FIRST DIAGRAM- SOURCE OF ENERGY AFTER A MEAL

2-4 hours ingested glucose
rest- glycogen

24 hours na-gluconeogenesis

WHAT CAN BECOME GLUCOSE?

Lactate! (CORI CYCLE)
All intermediate of glycolysis and krebs cycle except acetyl coa
INSTEAD CONVERT ACETYL COA TO KETONE BODIES-> HMG COA SYNTHASE
KHETTONESS

When you degrade triglycerides, glycerol, propionyl coa becomes glucose (STUDY)
SUPPLEMENT

Amino acids- glucogenic

Lysine and leucine lang

Starvation doesnt work

-lose water weight
-lose glycogen stores
-catabolize non-essential proteins
albumin vs globulin, albumin goes down first

check nutritional status, albumin. Globulin can remain high even while starving

no more fats- burn essential proteins!

Well-fed state/absorptive state

- Use glucose as fuel
- Liver replenishes its glycogen stores, replaces any needed hepatic proteins and
increases TAG synthesis
- Adipose: increased TAG synthesis and storage
- Muscle increase protein synthesis
- Brain uses glucose exclusively as fuel
In the absence of food

Liver: degrades glycogen, initiates gluconeogenesis using FA oxidation both as a source of

energy to supply

Up to 20% can be provided by ketone bodies

VITAMINS

Macronutrients- energy-rich molecules larger than that of the other dietary nutrients
-fats, carbs, proteins
-may include ethanol in some diets

Micronutrients
-nutrients needed in lesser amounts
-vitamins and minerals

Estimates average requirement

-average daily nutrient estimated to mee the requirement of 50 percent will meet

required daily allowance 95%

adequate intake- di nila alam,

tolerant upper intake- limit before exhibiting toxicity

Estimated energy requirement

Energy intake= energy expenditure

Carbs 45 to 65
Fat 20 to 35
Protein 10 to 35

Renal disease, lower protein intake, can be harmful to kidney

Energy content
9 kcal/gram fats
7 kcal/ gram alcohol
4 kcal/gram carbs

106- palmitate
ENERGY NEEDED TO METABOLIZE ALCOHOL- NOT SULIT!

Resting metabolic rate (60% Basal metabolic rate)

10% diet induced thermogenesis

- Digesting your food
- -increase in metabolic rate after a meal
- -YOU NEED ATP TO ABSORB GLUCOSE AND GALACTOSE

Kwashiorkor- protein
Marasmus- caloric deficiency
Why is there edema in kwashiorkor, protein loss, intravascular oncotic pressure inreases,
nothing holds water, fluid extravasates to interstitial fluid

More than 1 year old kwashiorkor

FAT SOLUBLE VITAMINS

ADEK
More toxic
KASI POLARITY IS NEEDED FOR EXCRETION

MEGA DOSES OF VIT C- IHI LANG

Absorption dpendent on ileum, bile and pancreas

Toxicity more common
Increased leads to storage
-steatthorea

Vit A
Retinol
Retinal
Retinoic acid

Cis-> trans retinal

-differentiation
retinol- gametogenesis in gonads
vit a deficiency is still the leading cause in preventable blindess
retinoic acid- growth regulators in the epithelium
first sign- nyctalopia ( night blindness)
cerophtalamia- eye and corneal dryness

TERATOGENIC IN HIGH DOSES

Isotretinoin- request for pregnancy test

Pesudortumor cerebri- raised intracranial pressure but no mass lesions

Vitamin D- 1,25 dihydroxy vitamin d calcitriol

Has 2 hidroxyl groups
HYDROXYLATION OF

HAPPENS IN 2 ORGANS, LIVER 25 HYDORXYLATION

KIDNEY 1
No hydroxylation, inative vitamin d
Renal failure- prone to vitamin d deficiency

Vitamin d is a hormone, important in calcium homesotatsis

Increases serum calcium and phosphate
Increase bone resorption
Increase intestinal absorption of ca
Increase kidney reabsorption

Parathyroid hormone- low phosphate

Chovstek sign-if you touch onfacial nerve, twitches involuntary
Trosseau sign- spam when you place

Prolonged QT

HYPERCALCEMIA
-Short QT
stone bones abdominal groans

child
rickets
adult-osteomalacia

vitamin e
-antioxidant in the lipid phase
-protects membrane lipids from peroxidation
-prevent oxidation of LDL, lowers atherogenesis

prevents LDL from depositing in arteries

deficiency
RBC fragility, hemolysis
-least toxic vitamin!!!!!!!!

Vitamin K 27910
-rare kasi produced by bacteria in the GIT
-Hemorrhagic disease of the newborn, sterile
-presents as bleeding
neonates at risk because of sterile GIT and low vitamin K content of breast milk
toxicity: jaundice + hemolytic anemia
BRAIN HEMORRHAGE!

WATER SOLUBLE
Vitamin B1
B2
B3
B5
B6
B12
C
BIOTIN
FOLATE 9
GENERALLY NON TOXIC 6, 12 AE MOST TOXIC
Thiamine pyrophosphate
-pyruvate dehydrogenase, alpha ketogultarate, and branched chain AA dehydrogenase
transketolase reaction in the HMP shunt

def: beriberi, nheart failure

polyneuritis
-symmetrical muscle wasting

THIAMINE DEFICIENCY IN ALCOHOLICS- hypoglycemic, vit B1 doffision

wernickes syndrome
ataxia (difficulty maintain balance)
opthalmoplegia

Korsakoff syndrome (memory problems)

-loss of memory
confabulation (making up stories)
seeing or hearing things that arent really there

Vitamin B2- riboflavin!

Flavin monoucleotide, FAD
-cofactor of akd

Niacin- NAD
Comes from
-tryptophan!
No pyridoxal phosphate, niacin deficiency
Pellagra (diarrhea, dermatitis, dementia)
Hartnup disease (decreased tryptophan absorption)
Carcinoid Syndrome (increase w metabolism), elevated levels of serotonin
Isoniazid use- decreased vitamin B6 (used to treat tuberculosis) Binds to vitamin b6

Panthothenic acid- coenzyme a

Used as cofactor for acyl transferases
-require fatty acids!

Pyridoxal Phospahte-
Used as coenzyme in AA transamination
-used for
glycogen phosphorylase (glycogenolysis)
cysthationine synthase
ALA synthase (heme synthesis)

Isoniazid inactivates vitamin b6

INH + pyridoxal phosphate- inactive derivative
Peripheral neuropathy
Synthesis of niacin from tryptophan

Excess, gait problems, CNS toxicity more than 2 g per day

Cobalt in center of corrin ring

Gastrectomy, deficiency of vitamin B12
-metabolism of cobalamin!
Methylmalonyl succinyl

Homocysteine back to methionine, B12 is needed

PERNICIOUS ANEMIA! FOLATE! COBALAMIN!

ONLY B12 DEFICIENCY HAS NEUROLOGIC SYMPTOMS
Subacute combined degeneration
Diagnosis- schilling test, vitamin b12, anti IF
Corticospinal tract dorsal columns

Folate
Pterin ring folic acid. Pterin ring _ para-aminobenzoic acid + glutamate residues
Thymidylate synthase- cancer
Humans cannot synthesize paba

CONTRAHEMOXASOLE-
Interferes with folate metabolism in becteria
WE CANNOT SYNTHESIS, MORE AFFINITY TO BACTERIA

Folic acid- 400 mcg perday

Anencephaly
Myelomeningocoele

Biotin
- CARBOXYLASE
FA SYNTHESIS FACCC acetyl coa carboxylase
Canbe induced by avidin in egg whites
20 egg whites a day
dermatitis
enteritis

vitamin c-
cofactor in collagen synthesis (hydroxylation of proline and lusine)
dopamine- beta hydroxylase (domaine to norepineprhine)
scurvy
reduces fe3 to fe2 to increase fe absorption

Minerals

Iron (3-4g), two thirss of which is in hemoglobin

Ferritin
-low
Hemosiderin
-partially denature dorm of ferritin
WHEN HIGH
Transferrin- tansport form in plasma

Iron
Heme synthesis, last
Incorporates iron in protoporphyrrin 9
Microcytic anemia

Hemochromatosis- seen mainly in older men

- Increased total plasma iton, transferrin, saturation, serum ferritin
- Treated by phlebotomy

Hemosiderosis- recurrentblood transfusion

Zinc- most abundant trace mineral after iron, 1.5-2.5

Alcohol dehydrogenase
Carboxypeptidase A and B (protein digestion)
DNA and RNA polymerases
Zinc finger proteins
Meats nuts beans

Zinc deficiency
-testicularl atrophy
Acotodermatitis (zinc)

Copper 80-110 mg in the human body

Superoxide dismutase 9free radical nneutralizaiton)
Dopamine hydroxylase
Tyrosinase melanin
Lysyl oxidase
-ceruloplasmin as transfer!!!!!!

Menkes syndrome, kinky hair, growth retardation

Unable to absorb copper properly

Wilson disease- sobra

-copper accumulation
-hepatolenticular degeneration
Presentation: laser flasier rings

Manganese- overdones- psychosis, parkinsonism

-can be replaced by mg

Molybdenum
-metabolism of purne (xanthine oxidase)

glutathione peroxidase-keshan disease- selenium

iodin-thyroid hormone
fluorine-teeth